Ghislaine Doufle? a and Niall D. Fergusona,b,c,d,e
Purpose of review
An increasing number of patients are placed on extracorporeal membrane oxygenation (ECMO) for respiratory or cardiac failure. Sound understanding of physiology and configuration of ECMO is essential for proper management. This review covers different monitoring parameters and tools for patients supported with different types of ECMO.
Emphasis is placed on monitoring saturations at different sites depending on type of ECMO support. The main monitoring tools detailed in this review are echocardiography and pulmonary artery catheters.
The review will help physicians better assess adequate ECMO support by using the appropriate parameters for each type of configuration.
echocardiography, extracorporeal membrane oxygenation, monitoring
A significant increase in the utilization of extracorporeal membrane oxygenation (ECMO) has occurred in the recent years and growing numbers of centers are using this life support modality. Although appealing, the technique is complex and evidence indicates that experience in managing patients on ECMO is a key determinant of outcome . A sound understanding of physiology and configuration is essential to ensure proper monitoring of patients supported with ECMO. Without a proper understanding of the patient’s specific ECMO configuration, even usual parameters such as arterial blood gases can be misleading and potentially expose the patient to hypoxic conditions. Specific monitoring of a patient supported with ECMO entails thorough clinical examination, inspection of the circuit, monitoring of hemodynamic and biological parameters, including but not limited to blood gases and coagulation profile. This review will cover different modalities for cardiopulmonary monitoring in ECMO patients.
Although the aim of this review is not to provide an exhaustive description of the different types of configurations, a brief overview will ensure proper understanding of ECMO physiology and related monitoring criteria discussed. Readers will be referred to other articles for further reading [2&&,3–5]. For clarity purposes, veno-venous ECMO and veno-arterial ECMO will be discussed separately.
MONITORING ON VENO-VENOUS
EXTRACORPOREAL MEMBRANE OXYGENATION
Physiology of veno-venous extracorporeal membrane oxygenation
Veno-venous ECMO is a modality employed for isolated respiratory failure. Blood is drained and reinjected in the venous system. Several configurations have been described ranging from femorofemoral, femorojugular, and single cannulation with double lumen catheters (Figs 1 and 2) [6&&]. After oxygenation and decarboxylation, the blood exiting the membrane is reinjected in the right atrium (RA) and ejected in the pulmonary circulation by the patient’s own cardiac function. Venovenous ECMO does not directly affect cardiac function. Indirect effects can be observed in presence of acute cor pulmonale secondary to respiratory failure and exacerbated by high ventilatory settings [7,8]. It is fairly common to observe a significant improvement of hemodynamic parameters immediately after institution of veno-venous ECMO in this setting . Nonetheless, in absence of right ventricular
aInterdepartmental Division of Critical Care Medicine, University of Toronto, bExtracorporeal Life Support (ECLS) Program, Toronto General Hospital, cDepartments of Medicine, Physiology, and Institute for Health Policy, Management and Evaluation, University of Toronto, dToronto General Research Institute and eDepartment of Medicine, Division of Respirology, University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada
Correspondence to Ghislaine Doufle?,Toronto General Hospital, University Health Network 585 University Ave, PMB 11-120, Toronto, Ontario M5G
2N2, Canada. Tel: +1 416 340 4800 x5061; fax: +1 647 776 3148;
Curr Opin Crit Care 2016, 22:000–000
Significant differences in monitoring saturation exist between veno-venous and veno-arterial ECMO.
Knowledge of ECMO configuration and determinant of pressure of oxygen at different sites is essential for appropriate monitoring and management.
Echocardiography is an invaluable tool for both venovenous and veno-arterial ECMO, and should be performed by a physician with sound knowledge of ECMO physiology.
FIGURE 1. VV and VA ECMO configurations and corresponding echocardiographic views. Diagram showing the most common ECMO configurations in our center. 1. Bicannulation VV ECMO (femorojugular cannulation) with drainage cannula in the femoral vein and the reinjection in the SVC, via the jugular vein. (a) Mid esophageal view showing the SVC and reinjection cannula within it (TEE). (b) IVC subcostal view, the drainage cannula is visualized within the IVC in long axis (TTE). 2. Femorofemoral VA ECMO cannulation. The drainage cannula is located in the IVC and the reinjection cannula is in the iliac artery/distal descending aorta. (c) Transthoracic apical 4 chamber of a patient with a dilated cardiomyopathy. The cannulae are not visualized on this view but note the presence of an automatic implantable cardioverter defibrillator within the right ventricle. Used with permission. Reproduced from [6 &&]. CO2, carbon dioxide; ECMO, extracorporeal membrane oxygenation; IVC, inferior vena cava; SVC, superior vena cava; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography; VA, veno-arterial; VV, veno-venous.
FIGURE 2. Bicaval dual lumen cannula for VV ECMO (Avalon Elite) and corresponding echocardiographic views. This picture depicts a bicaval dual lumen cannula, inserted via the internal jugular vein. The drainage holes are located in the SVC and IVC, and the reinjection hole is facing the tricuspid valve. (a) Mid esophageal bicaval view showing the cannula within the RA (TEE). (b) Transthoracic subcostal view showing the cannula in the RA, the tip of the cannula is located in the IVC. The reinjection hole is visible, oriented towards the TV. Reproduced from [6&&]. CO 2, carbon dioxide; ECMO, extracorporeal membrane oxygenation; IVC, inferior vena cava; RA, right atrium; SVC, superior vena cava; TEE, transesophageal echocardiography; VV veno-venous.
(RV) dysfunction veno-venous ECMO will not provide any hemodynamic support.
Veno-venous ECMO allows physicians to separately titrate oxygenation and carbon dioxide clearance.Oxygenationdependsmainlyontheratio of blood flow through the ECMO circuit relative to the patient’s cardiac output (CO), whereas carbon dioxide elimination depends on flow of gas through the oxygenator, referred to as sweep gas flow . Other factors can influence oxygen transfer through the membrane to a more limited extent, including inspired fraction of oxygen in the gas flow through the membrane, membrane lung properties, time of exposure of blood in the membrane, hemoglobin concentration, and gradient of gases across the membrane. The combination of those factors determines the rated flow or maximal oxygen delivery, which is the amount of desaturated blood that can be fully saturated per minute .
To allow optimal oxygenation, ECMO flows must represent a significant proportion of the patient’s CO. This can be achieved by increasing ECMO flows in an attempt to match patient’s CO or by decreasing the patient’s CO . It has been shown that flows equating 60% of the patient’s CO were usually sufficient to maintain arterial oxygen saturation above 90% . Carbon dioxide clearance is more effective than oxygenation because of the higher solubility and diffusivity of carbon dioxide, and can be titrated by increasing or decreasing the sweep gas flow. Shortly after ECMO initiation, respiratory system compliance is often extremely low and the patient’s native pulmonary function is almost negligible. During that phase, all gas exchange is supported with ECMO. Recommendations of ventilatory strategies on ECMO suggest ventilatory settings allowing lung rest [11,13]. In the recovery phase, respiratory compliance improves and the patient’s pulmonary function also contributes to arterial oxygenation and carbon dioxide clearance.
MONITORING OF BLOOD GASES
Arterial blood gases
Monitoring of arterial oxygen saturation on venovenous ECMO does not differ from any other patient.Apulse oximeter canbe placedinterchangeably on both arms and arterial blood gases drawn from either side. As the blood is traveling using the normal pathway, there should not be any substantialdifferencebetweensides.Arterialpartialpressure of oxygen is determined bymixed venoussaturation (SvO2) and intrapulmonary shunt. Thus in the early phase, when lung function may be almost nonexistent (shunt fraction being equal to 100%), partial pressure of oxygen is very close to SvO2 . Arterial oxygensaturationabove85%isacceptableaslongas oxygen delivery is adequate. Oxygen delivery/oxygen consumption ratio (DO 2/VO2) should be maintained above 3 to avoid tissue hypoxia [11,13,14]. Some centers tolerate even lower levels of saturation, whereas targeting a higher hemoglobin level (12g/dl) to optimize oxygen delivery, which is still the target recommended in the ELSO guidelines . One may advocate against this higher threshold as transfusion in the critical care population has been shown to worsen outcome. In addition, lower levels of 2,3 diphosphoglycerate in transfused blood and subsequent increase of hemoglobin affinity for oxygen may limit oxygen uptake. In our center, we tolerate saturations as low as 85% while aiming for a hemoglobin level above 8g/dl. There is no published study comparing these approaches,although arecentlypublished report on blood conservation protocol on ECMO showed similar outcome [16&&]. In this study, they tolerated hemoglobin levels as low as 7g/dl in combination with saturation above 92% (Table 1).
In the recovery phase, pulmonary shunt and dead space must be accounted for to obtain arterial saturation and arterial pressure of carbon dioxide level. Estimation of the shunt fraction remains cumbersome and requires a pulmonary catheter. Some authors recommend daily monitoring of the shunt fraction, although this is not something we do in routine clinical practice .
Venous blood gases
Table 1. Parameters monitored on veno-venous and veno-arterial extracorporeal membrane oxygenation and their main determinants
DO2/VO2, oxygen delivery/oxygen consumption ratio; ECMO, extracorporeal membrane oxygenation; PaO2, arterial pressure of oxygen; PCO2, pressure of carbon dioxide; PO2, pressure of oxygen; ScVO2, central venous saturation; SVC, superior vena cava; SVO2, mixed venous saturation.
In normal conditions, measurements of central or mixed venous saturation allow physicians to assess adequacy of oxygen delivery in relationship to oxygen demand. However, on veno-venous ECMO venous saturation as measured in the RA or pulmonary artery does not represent the true venous saturation. Thus, venous saturation may not be suitable to assess (DO2/VO2) adequacy. Indeed a variable portion of the blood is reinfused from the ECMO circuit, and therefore contains highly oxygenated blood. Venous saturation on ECMO represents a mixture of blood coming from systemic venous return and from the ECMO circuit.One can estimate the resulting venous saturation by knowing the oxygen content of the venous blood, the oxygen content of the blood coming from the ECMO, and the respective proportion of ECMO blood to venous return [2&&]. Some centers use the blood from the drainage line of the ECMO circuit (premembrane blood gases or inlet blood gases) as a surrogate for mixed venoussaturation.Inabsenceofrecirculation premembrane blood gases remain a good reflection of central/mixed venous saturation, and levels above 75% indicate adequacy of oxygen delivery/ consumption. Some centers use continuous monitoring of mixed venous saturation to calculate systemic VO2 and DO2 in addition to ECMO VO2 and follow them over time to assess recovery . Others continuously monitor inlet and outlet blood gas saturation and calculate oxygen transport and oxygen consumption via ECMO [3,15].
Nevertheless, since the blood is drained and reinfused in the same chamber there is potential for recirculation. Recirculation represents the fraction of blood reinjected into the RA and immediately suctioned back into the drainage cannula [18&&]. This recirculation fraction is not available for systemic oxygenation and may contribute to ineffective ECMO and hypoxemia. Gross recirculation can be diagnosed by observing a sudden change ofcolorinthedrainage cannulaalternatingbetween oxygenated and deoxygenated blood. Macroscopic recirculation occurs when drainage and reinjection cannulae are too close to one another, ECMO drainage suction is too high or alternatively when CO is critically low. ECMO flows should be decreased or attempt to increase CO initiated. Double lumen catheters present less potential for recirculation
Recirculation fraction can be estimated with a formula integrating premembrane, post membrane, and mixed venous saturations:
Recirculation fraction: (SpreO2SvO2)/(Spost O2SvO2)100
This equation requires a true SvO2, only obtainable when the sweep gas is totally interrupted, which may not be tolerated in the early phase of ECMO support [18&&,19–22]. Other methods use blood from the superior vena cava (SVC) or the inferior vena cava (IVC) as a surrogate, rendering the calculation less accurate. Therefore, other mathematical models have been developed in vitro to try to estimate recirculation fraction . Ultrasound dilution technique has also been described to quantify amount of recirculation. This technique allows calculation of recirculation fraction without SvO2. It is based on ultrasound velocity properties and dilution of blood. It requires two sensors, one placed on the drainage limb of the circuit, one on the reinjection. Dilution of blood will change the ultrasound velocity . After injection of saline, changes in velocity will be detected by the sensors and generate a dilution curve for each limb of the circuit. The ratio of the area under the curve will represent the recirculation fraction. If there is no changeinvelocityinthedrainagelimb,thenthereis no recirculation. Those techniques have not gained widespread use. Most centers still use increased oxygen saturation and its trend over time in the premembrane blood gases as a marker for recirculation.
Postmembrane or outlet blood gases
The membrane lung is also subject to shunt and dead space fractions, which will worsen with time, as progressive thrombosis and fibrin formation will deposit in the membrane . This will be associated with progressive decline in oxygen and carbon dioxide transfer over time. Proper function of the membrane usually allows to obtain outlet pressure of oxygen above 300mmHg . Postmembrane pressure of oxygen should be monitored regularly as significant deterioration in membrane performance may cause hypoxemia and warrant a change of the membrane. Carbon dioxide clearance is usually maintained but may require higher sweep gas flow.
Although, routinely used in some centers the place of the pulmonary artery catheter in venovenous ECMO patients remains in our opinion, questionable [17,24]. Firstly, SVO2 is influenced not only by the oxygen delivery/consumption ratio but also by ECMO flows. Additionally, it is unclear on how flows to and from the RA impact calculation of CO with the thermodilution technique. As vascular resistance is also derived from measurement of CO and cardiac pressure, it is debatable if those calculations remain accurate.
As previously mentioned, veno-venous ECMO does not directly affect cardiac function. Therefore, normal or subnormal cardiac function is usually present in most patients. Indications for echocardiography to monitor cardiac function itself are guided by clinical context, as deemed necessary by the attending physician.
However, echocardiography in patients supported with veno-venous ECMO presents specific indications [6&&,25–28]. Optimal cannula positioning is crucial for adequate oxygenation. It is recommended that the cannula’s tip sits in the RA (just beyond the IVC/RA junction, ensuring a safe distance from the interatrial septum and tricuspid valve). If the drainage cannula is too distant from the IVC RA junction, appropriate flows may not be obtained because of collapse of the vein around the cannula, especially in case of decreased intravascular volume, or when patients initiate spontaneous breathing. As a consequence, it may hinder maintenance of restrictive fluid strategy, as fluid may need to be administered to restore adequate flows . On the other hand, if the cannulae are too close, recirculation may become an issue. Thus, appropriate cannula position should be ascertained not only with chest radiograph but also with echocardiography, as chest radiography does not allow visualization of the distance between the tip of the cannula and IVC/RA junction .
Inadequate flows may also be because of thrombusformationwithinthecannula,whichcanalsobe identified with echocardiography .
In addition, presence of pericardial and pleural effusion should be noted, and monitored as anticoagulation may potentially worsen them.
Double lumen catheters present specific challenges inherent to their design. The lumen dedicated for blood drainage displays two sites: proximal, which should be positioned in the SVC, while the distal tip should be in the IVC. The second lumen containing the oxygenated blood terminates via an orifice sitting in the RA. Optimal position of the reinjection orifice is the mid-RA, facing the tricuspid valve . Double lumen catheters are prone to dislodgment with potential deleterious consequences on oxygenation . When the cannula migrates too deep intotheIVC,reinjectionmaybeinthehepaticvein. Conversely, if the cannula is too far out, reinjection flow will be within the SVC. Additionally, if the flow is directed toward the interatrial septum, oxygenation may become suboptimal. In all cases, oxygenation may be compromised. Chest radiograph is not sufficient to ascertain proper position of the cannula as it does not allow to identify the different portions of the cannula and their relative position to cardiac structures. Echocardiography is best suited to identify the precise positioning of each portion of the cannula [33,34]. Therefore, in presenceofpersistenthypoxemia,lowECMOflows, thecannula’slocationshouldbeverifiedwithechocardiography. Transthoracic views are usually adequate, but transesophageal echocardiography may be warranted. Both tip and reinjection orifice are usually easily identified, either on the subcostal and parasternal views (RV inflow and inflow outflow view on transthoracic echocardiography) or in the mid esophageal bicaval view (transesophageal echocardiography). Cannula repositioning under echo guidance should be considered in case of malpositioning and impaired oxygenation. To betterguidethepositioning, echocardiography should be performed by an operator accustomed to performing echocardiography in ECMO patients, as some alternative views may be required to properly visualize all portions of the cannula . Additionally, color flow Doppler may help identify the appropriatedirectionofthereinjectionflowtoward the tricuspid valve.
During the weaning phase, unless hypoxemia and hypercarbia precipitate RV dysfunction, there should not be any change in cardiac function, thus indications for echocardiography are guided by clinical and hemodynamic status.
MONITORING ON VENO-ARTERIAL
EXTRACORPOREAL MEMBRANE OXYGENATION
Physiology of veno-arterial extracorporeal membrane oxygenation
Veno-arterial ECMO provides both cardiac and pulmonary support. Blood is also drained from the venous system but reinjected in the arterial system either centrally (reinjection cannula in the ascending aorta in adults) or peripherally via the femoral artery (Fig. 1). On peripheral veno-arterial ECMO, when the patient’s cardiac function is severely depressed, high ECMO flows will ensure complete cardiac and pulmonary support. Blood reinfused by the ECMO reaches the ascending aorta and perfuses all the organs in a retrograde fashion. As blood travels from iliac artery to the ascending aorta oxygen uptake along the aorta results in a progressive decrease in arterial partial pressure of oxygen. If left ventricular function is not completely depressed, and the left ventricle (LV) still manages to eject a significant stroke volume, there will be mixing of blood within the aorta. The exact location of the mixing is unpredictable and depends on ECMO flows, vascular resistance, and the patient’s intrinsic ventricular function. If respiratory function is preserved and in absence of pulmonary edema, this phenomenon has little consequence. On the other hand, if pulmonary function is impaired, it can result in poor oxygenation of the most proximal branches of the aorta, namely coronary arteries and head vessels (Fig. 3) . This can potentially expose the patient to coronary and cerebral hypoxia. The extreme manifestation of this phenomenon is described as ‘Harlequin syndrome’ with clinically identifiable differential oxygenation: concomitant cyanosis of the upper body with normal oxygenation of the lower body. Some authors reported the use of near infrared spectroscopy to monitor cerebral function on ECMO. Any decrease in cerebral oxygenation prompted implementation of therapeutic measures, including reposition of patient or cannula, titration of ECMO flows to optimize oxygen delivery, and neuroimaging if persisting cerebral hypoxia. In their cohort, all patients who exhibited refractory alteration in cerebral tracings had confirmed cerebral events on imaging .
FIGURE 3. Mixing of blood in ascending aorta on peripheral VA ECMO. Picture depicting ‘Harlequin’ syndrome on peripheral VA ECMO and differential saturation at different sites of the ascending aorta. This diagram highlights the importance of monitoring arterial saturation from the right side on peripheral VA ECMO. ECMO, extracorporeal membrane oxygenation; PaO2, arterial pressure of oxygen; VA, veno-arterial.
MONITORING OF BLOOD GASES
Arterial blood gases
On peripheral veno-arterial ECMO, it is crucial to monitor oxygenation as far as possible from the reinjection site. An arterial line should ideally be placed on the right arm, and blood gases taken from the right side. Arterial blood gases drawn on the left side or worse on a femoral artery could be completely discrepant from oxygenation at the level of coronary, innominate, and left common carotid arteries (Table 1).
When an arterial line cannot be placed on the right side at least a pulse oximeter should be placed on the right side, though this can also be a challenge if intrinsic CO is very low as the ECMO flow is nonpulsatile.
The underlying disease will dictate the appropriatemanagementinpresenceofsignificantdifferential oxygenation.Pulmonaryedemasecondarytoleftventricular distension may subside by venting of the left atrium[37–40].Addingaveno-venouscomponentfor aveno-venousarterialconfigurationmaybeindicated in case of concomitant pulmonary disease.
The aforementioned phenomenon is not an issue with central cannulation as proximity of reinjection from the coronaries and anterograde direction of blood flow do not usually cause significant competition.
Venous blood gases
Unlikeonveno-venousECMO,venoussaturationon veno-arterial ECMO is a true reflection of venous oxygen content. Indeed, there is no recirculation on veno-arterial ECMO since there is no communicationbetween drainageandreinjection sites. Therefore, venous saturation, measured either from a central line or premembrane blood gases is highly valuableto ensure thatoxygen deliveryis adequately matched to oxygen consumption. Continuous in-line venous saturation monitors incorporated in the circuit are available and may help guide management, allowing instantaneous readjustment of therapy. A low venous saturation should be addressed as for any critically ill patient. In presence of concomitant hyperlactatemia and signs of endorgan hypoperfusion, the first step should usually be to increaseECMO flowstooptimize oxygen delivery. Ifpersistentlylow,optimizationofvolumestatusand possibly transfusion may be warranted.
Pulmonary artery catheter/cardiac output measurement
Similar to veno-venous ECMO, it is unknown how veno-arterialECMO affects degreeoftricuspid regurgitationandCOmeasurementwiththermodilution. However, pulmonary artery occlusion pressure and mixed venous saturation are not affected by venoarterial ECMO. Pulse pressure contour analysis methods may be limited by decreased pulsatility. There are, to our knowledge, no reported studies of pulse contour analysis technique in ECMO patients.
Echocardiography on veno-arterial extracorporeal membrane oxygenation
Echocardiographic monitoring on veno-arterial ECMO is paramount [6&&,35]. Each study performed should be reported with mention of hemodynamic parameters, dose of vasoactive drugs and ongoing flows,asthis willserveasreferenceto assess recovery if and when it occurs. In addition, assessment of size and function of both ventricles is greatly affected by ECMO flows. Appropriate unloading of the right ventricle should be ensured, by checking cannula position and RV size. It is difficult to know how veno-arterial ECMO may influence the degree of tricuspid regurgitation and estimation of pulmonary artery pressure. Left ventricular size should also be assessed as progressive distension may induce pulmonary edema.
As in veno-venous ECMO, proper cannula positionshouldbeascertained,andintracannulathrombus and pericardial effusion ruled out. Diagnosis of pericardial tamponade can be difficult in ECMO patients and should remain a clinical diagnosis. For instance,presenceofpericardial effusionwithpartial chamber collapse on veno-arterial ECMO may be delicate to interpret under high flows.
Additionally, opening of the aortic valve should be documented using echocardiography. It usually coincideswithpulsatilityonarteriallinetracing,but echocardiography allows a direct visualization of the valve. Presence of spontaneous echo contrast or thrombi in the LV or aorta can also be seen on echocardiography [41–43]. Whether presence or absenceofpulsatilityislinkedtooutcomeisunclear. Nevertheless, when the aortic valve remains closed, there is higher risk for thrombosis [41–43]. Therefore, therapies are usually implemented to allow opening of the valve. Reducing vascular resistance or ECMO flows may allow more consistent opening of the valve. Some authors have suggested the concomitant use of intra-aortic balloon pump or microaxial pump to decrease the LV afterload [44–49]. When severe pulmonary edema is present, left atrial venting has been proven effective to alleviate pulmonary congestion [37–40,45,50].
Presence and severity of aortic and mitral regurgitation should be noted. Increased afterload can aggravate aortic regurgitation and subsequently worsen LV distension, with potential subendocardial ischemia hindering recovery [51–53]. Mitral regurgitation will worsen pulmonary edema.
When signs of cardiac recovery are present, (i.e., higher pulsatility and maintained hemodynamics with decremental flows) quantification of cardiac function whereas lowering flows allow assessment of recovery. Some authors have used aortic velocity integral and tissue Doppler at the mitral annulus to predict successful weaning [54&,55,56]. To test if the patient can be weaned off ECMO, flows are decreased transiently to approximately 1l/min, while assessing size and function of both ventricles.
Flows are usually not decreased further in fear of circuit thrombosis. If biventricular function and hemodynamics are maintained despite low flows, the patient is deemed weanable. Specific attention should be paid to RV size and function, as even a low flow can mask dysfunction.
In summary, cardiopulmonary monitoring of patients on ECMO is unachievable without proper understanding of the type of ECMO configuration. Even blood gases measurements can be misleading if not integrated in clinical context. Echocardiography is an invaluable tool in managing patients on ECMO, but does also require proper knowledge of the patient’s configuration and should be integrated within clinical context.
The authors would like to thank Dr Alberto Goffi for his contribution with the figures.
Financial support and sponsorship None.
Conflicts of interest
There are no conflicts of interest.
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Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest
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