Intraoperative Management of Adult Patients on Extracorporeal Membrane Oxygenation: An Expert Consensus Statement From the Society of Cardiovascular Anesthesiologists—Part I, Technical Aspects of Extracorporeal Membrane Oxygenation : Anesthesia & Analgesia

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Intraoperative Management of Adult Patients on Extracorporeal Membrane Oxygenation: An Expert Consensus Statement From the Society of Cardiovascular Anesthesiologists—Part I, Technical Aspects of Extracorporeal Membrane Oxygenation

Mazzeffi, Michael A. MD, MPH, MSc, FASA*; Rao, Vidya K. MD; Dodd-o, Jeffrey MD, PhD; Del Rio, Jose Mauricio MD§; Hernandez, Antonio MD, MSc; Chung, Mabel MD, MPH; Bardia, Amit MD#; Bauer, Rebecca M. MD**; Meltzer, Joseph S. MD††; Satyapriya, Sree MD‡‡; Rector, Raymond CCP§§; Ramsay, James G. MD∥∥; Gutsche, Jacob MD¶¶

Author Information
Anesthesia & Analgesia 133(6):p 1459-1477, December 2021. | DOI: 10.1213/ANE.0000000000005738

Abstract

See Article, p 1456

BACKGROUND

Extracorporeal membrane oxygenation (ECMO) provides temporary circulatory and respiratory support for patients with refractory cardiopulmonary failure. Since the first use of ECMO in an adult in 1972, technology has improved, and valuable experience has been gained caring for patients. According to the extracorporeal life support organization (ELSO), over 60,000 adults at 500 ECMO centers worldwide have been treated with ECMO since 1990.1,2

Contemporary in-hospital mortality for venoarterial (VA) ECMO patients is 56% and for venovenous (VV) ECMO patients is 40%.2 Given the expanded use of ECMO in adults, which was further highlighted during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, the Society of Cardiovascular Anesthesiologists sought to create an expert consensus statement, which reviews technical aspects of ECMO and provides recommendations for anesthesiologists who manage ECMO patients. The expert consensus statement is not intended to supersede existing guidelines for management of ECMO patients in the intensive care unit, which have been published by ELSO, but rather provide guidance for management of ECMO patients during the intraoperative and immediate perioperative period. In the first part of this 2-part series, technical aspects of ECMO are discussed, and related expert consensus statements are provided.

METHODOLOGY

The Society of Cardiovascular Anesthesiologists Quality, Safety, and Leadership ECMO working group was composed of 12 cardiovascular-critical care anesthesiologists from adult ECMO centers in the United States. One perfusionist-ECMO manager was included in the writing group to enhance expertise on technical aspects of ECMO. In the first stage of creating the expert consensus statement, topics related to technical aspects of ECMO were proposed by group members. A literature review for each topic was performed using MEDLINE, and articles published after 1980 were included at the discretion of group members. The specific search terms that were queried varied for each topic area.

After completion of the literature review, group members drafted expert consensus statements that were submitted for consideration by the full working group. Each consensus statement was evaluated by all group members using a modified Delphi method, where group members used a 5-point Likert scale to evaluate statements. Consensus statements that 10 or more working group members “agreed” with, or “strongly agreed” with, were adopted into the final expert consensus statement. The methodology used was based on prior expert consensus statements from the Society of Thoracic Surgeons.3

BASIC PRINCIPLES, PATIENT SELECTION, AND INDICATIONS FOR VA AND VV ECMO

Venoarterial Extracorporeal Membrane Oxygenation

VA ECMO is used to support patients with cardiac failure from multiple etiologies (Table 1).4–13 VA ECMO provides gas exchange and circulatory support, with blood drawn from the venous system, pumped through an oxygenator, and returned to the patient’s arterial system. In cardiogenic shock, VA ECMO restores end-organ perfusion and mitigates the adverse effects of high-dose vasopressors and inotropes. The impact of VA ECMO on coronary artery perfusion and myocardial oxygen consumption depends on the cannulation strategy and whether left ventricular venting is performed.14 VA ECMO increases cardiac afterload and does not reduce preload to the same degree as cardiopulmonary bypass (CPB) because there is no blood reservoir and the heart cannot be emptied to the same degree.15 Because there is no blood reservoir with VA ECMO, lower levels of anticoagulation are used. Also, since there is no recycling of field blood and no air-blood interface, the inflammatory response to ECMO is less severe compared with CPB.16,17

Table 1. - Adult ECMO Indications
Indication
VA ECMO VV ECMO
Acute cardiogenic shock Acute respiratory failure (hypoxemic, hypercapnic, or combined)
 ARDS from multiple causes: pneumonia, trauma, pancreatitis, aspiration, inhalational injury, post cardiotomy
 COPD exacerbation
 Severe asthma
Decompensated end-stage lung disease
 Ischemia or myocardial infarction
 Myocarditis
 Septic cardiomyopathy
 Toxin-associated cardiogenic shock
 Post cardiotomy shock
 Structural heart disease
 Massive pulmonary embolism
 Primary graft dysfunction after heart transplantation
 Peripartum cardiomyopathy
 Amniotic fluid embolism
 Bridge to transplant for IPF, sarcoid, cystic fibrosis, etc
Other indications
 Bronchopleural fistula
 Primary graft dysfunction after lung transplantation
 Pulmonary alveolar proteinosis causing hypoxemia
 Massive pulmonary hemorrhage
 Management of extremely difficult airway
Procedural
 Complex thoracic surgery including airway surgery
Decompensated end-stage CHF
 Bridge to transplant for NICM or ICM
Resuscitation
 Cardiac arrest/ECPR
Procedural
 Circulatory support during ventricular tachycardia ablation
 Complex thoracic surgery including mediastinal mass resection
 Intraoperative circulatory support during lung transplantation
Abbreviations: ARDS, acute respiratory distress syndrome; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; ECMO, extracorporeal membrane oxygenation; ECPR, extracorporeal cardiopulmonary resuscitation; ICM, ischemic cardiomyopathy; IPF, interstitial pulmonary fibrosis; NICM, nonischemic cardiomyopathy; VA, venoarterial; VV, venovenous.

VA ECMO improves survival in patients with cardiogenic shock from myocardial infarction and can be used to support patients with postinfarction complications, such as ventricular septal defect or severe mitral regurgitation due to papillary muscle rupture.18,19 Increasingly VA ECMO is used to support patients having high-risk procedures including ventricular tachycardia ablation and complex thoracic mass resection.20–22 VA ECMO is also used to bridge patients to durable left ventricular assist device (LVAD) implantation or cardiac transplantation and in the management of primary graft dysfunction after heart transplantation.23–26 VA ECMO can be used to support patients undergoing lung transplantation and, in some centers, is the preferred technique.27–29

Table 2. - Mortality Prediction Models for ECMO Patients
Model/score First author and year of publication ECMO type Patient population Variables included AUROC
ENCOURAGE Muller et al (2016)31 VA Acute myocardial infarction Age >60 0.84
Female sex
BMI >25 kg/m2
GCS <6
Creatinine >150 μmol/L
Lactate <2, 2–8, >8 mmol/L
Prothrombin activity <50%
SAVE Schmidt et al (2015)32 VA Cardiogenic shock of any etiology Cardiogenic shock diagnosis type 0.68–0.90
Age
Weight
Pre-ECMO organ failure
Chronic renal failure
Duration of intubation before ECMO
Peak inspiratory pressure ≤20 cm H2O
Pre-ECMO arrest
Diastolic blood pressure before ECMO ≥40 mm Hg
HCO3 before ECMO ≤15 mmol/L
RESP Schmidt et al (2013)33 VV Acute respiratory failure of any etiology Age 0.74–0.92
Immunocompromised status
Duration of mechanical ventilation before ECMO
Cause of respiratory failure
Central nervous system dysfunction
Acute-associated nonpulmonary infection
Neuromuscular blockade or nitric oxide use
Bicarbonate infusion
Cardiac arrest before ECMO
Arterial partial pressure of carbon dioxide
Peak inspiratory pressure
PRESERVE Schmidt et al (2013)33 VV Acute respiratory distress syndrome Age 0.89
BMI
Immunocompromised status
Prone positioning
Days of mechanical ventilation
SOFA
Plateau pressure
Positive end-expiratory pressure
Abbreviations: AUROC, area under receiver operating characteristic curve; BMI, body mass index; ECMO, extracorporeal membrane oxygenation; ENCOURAGE, prediction of cardiogenic shock outcome for acute myocardial infarction patients salvaged by VA-ECMO; GCS, Glasgow coma score; PRESERVE, predicting death for severe ARDS on VV-ECMO; RESP, respiratory ECMO survival prediction; SAVE, survival after veno-arterial ECMO; SOFA, sepsis-related organ failure assessment; VA, venoarterial; VV, venovenous.

Multiple prediction models for mortality are published and are helpful in evaluating potential candidates for VA ECMO (Table 2).30 Area under the receiver operating characteristic curve (AUROC) analysis is used to assess how well a model discriminates between patients who will and will not have a particular outcome (eg, mortality). For mortality prediction models, higher AUROCs reflect that a model can effectively discriminate between patients who will die versus survive. Models that have an AUROC >0.8 are considered to have good discrimination, and models that have an AUROC >0.9 are considered to have excellent discrimination. The prediction of cardiogenic shock outcome for acute myocardial infarction patients salvaged by VA-ECMO (ENCOURAGE) score predicts mortality for patients with myocardial infarction, who are supported with VA ECMO, and has an AUROC of 0.84, indicating good discrimination.31 The survival after veno-arterial ECMO (SAVE) score is a score that predicts mortality for VA ECMO patients with cardiac failure from multiple etiologies and has an AUROC of 0.68 to 0.90, depending on the patient population.32

Venovenous Extracorporeal Membrane Oxygenation

VV ECMO is used to support patients with hypoxemic, hypercarbic, or combined respiratory failure from multiple etiologies (Table 1). VV ECMO provides gas exchange, but not circulatory support, as blood is drawn from the venous system, pumped through an oxygenator, and is returned to the patient’s venous system. The most common indication for VV ECMO is acute respiratory distress syndrome (ARDS). Contemporary mortality for severe ARDS without VV ECMO is near 50%, while mortality with VV ECMO is closer to 35% when the results of multiple studies are pooled.34,35 In 2018, the results of the ECMO for severe ARDS trial, which was a randomized controlled trial of VV ECMO for ARDS, were published. In this study, VV ECMO did not significantly reduce 60-day mortality, relative risk = 0.76 (95% confidence interval [CI], 0.55–1.04).36 However, there were some better outcomes in patients who received VV ECMO, including fewer strokes. Also, a large percentage of patients in the control group, received salvage ECMO, which may have led to an underestimation of its mortality benefit. When these data are considered in conjunction with the results of multiple observational studies, it is likely that VV ECMO modestly reduces mortality in patients with severe ARDS.36–38

VV ECMO has been used to bridge patients to lung transplantation or to support post lung transplant patients with primary graft dysfunction.39–43 Less common indications include inhalation injury, traumatic lung injury, and bronchopleural fistula.44–47 In cases of right ventricular failure and acute respiratory failure, a right ventricular assist device can be combined with an oxygenator to provide VV ECMO and right ventricular support.48 To provide right ventricular support, blood must be returned from the ECMO circuit distal to the pulmonic valve. This configuration is sometimes referred to as venopulmonary arterial (“V-PA ECMO”). Several prediction scores exist for mortality in VV ECMO patients (Table 2), but the 2 most commonly used are the respiratory ECMO survival prediction (RESP) score (AUROC = 0.74) and predicting death for severe ARDS on VV-ECMO (PRESERVE) score (AUROC = 0.89), which have similar discrimination.33,49,50

ECMO CIRCUIT COMPONENTS

The key components of an ECMO circuit are the blood pump, membrane oxygenator, air-oxygen blender, heat exchanger, cannulas, and tubing. ECMO can be performed centrally with cannulation of the heart and great vessels or peripherally with cannulation of peripheral veins and arteries. Schematics of common VA and VV ECMO configurations are shown in Figures 1–3. Examples of 2 different ECMO circuits and consoles are shown in Figures 4 and 5. Different consoles display different information, which may include measured ECMO circuit blood flow, measured venous pressure, measured preoxygenator pressure, measured postoxygenator pressure, calculated pressure drop across the oxygenator (Δp), and measured blood temperature.

F1
Figure 1.:
A right common femoral vein-right common femoral artery peripheral VA ECMO configuration. Reprinted with permission from Ramsay et al.51 ECMO indicates extracorporeal membrane oxygenation; VA, venoarterial.
F2
Figure 2.:
Dual cannulation VV ECMO with cannulation of the right common femoral vein and right internal jugular vein. Reprinted with permission from Ramsay et al.51 ECMO indicates extracorporeal membrane oxygenation; VV, venovenous.
F3
Figure 3.:
Single cannulation VV ECMO using a dual lumen cannula in the right internal jugular vein. Reprinted with permission from Ramsay et al.51 ECMO indicates extracorporeal membrane oxygenation; VV, venovenous.
F4
Figure 4.:
A, Cardiohelp ECMO system (Getinge Group) and (B) Cardiohelp console. Red arrows indicate various circuit components and different variables that are displayed on the console. ECMO indicates extracorporeal membrane oxygenation; RPM, revolutions per minute.
F5
Figure 5.:
A, Novalung Heart and Lung Therapy System (Xenios AG) and (B) Novalung Heart and Lung Therapy System console. Red arrows indicate various circuit components and different variables that are displayed on the console. RPM indicates revolutions per minute.
F6
Figure 6.:
A CRRT circuit connected to an ECMO circuit. The CRRT drainage tubing and return tubing are connected post pump and preoxygenator so that the driving force of the pump can be utilized, and air entrainment is minimized. CRRT indicates continuous renal replacement therapy; ECMO, extracorporeal membrane oxygenation.
Table 3. - Commonly Used ECMO Pumps
Details Rotaflow RF-32 CentriMag acute circulatory support system Cardiohelp HLS Xenios DP3 LifeSPARC
Manufacturer Getinge Group Abbot Cardiovascular Getinge Group Xenios AG TandemLife
Type of pump Centrifugal Centrifugal Centrifugal Rotary diagonal flow pump Centrifugal
Type of support VA, VV VA, VV VA, VV VA, VV VA, VV
Maximum blood flow 9.9 LPM 9.9 LPM 5 or 7 LPM depending on model 8 LPM 8 LPM
Maximum RPMs 5000 5500 5000 10,000 7500
Emergency back up during power failure Hand crank No hand crank, backup console required Hand crank No hand crank, backup console, or battery exchange required No hand crank, backup console, or battery exchange required
Disposables cost $ $$$ $$$ $$ $$$
Unique features Magnetically-levitated rotor with a single bearing, which may mitigate hemolysis Magnetically-levitated rotor without bearings, which may reduce hemolysis Integrated pump, oxygenator, and heat exchanger Partial oxygenation/CO2 removal (PECLA): pumpless arteriovenous configuration relies on a patient’s native cardiac output to drive blood flow from femoral artery through the oxygenator and into a central vein Magnetic pivot bearing
Allows for rapid priming with priming tray in 3 min
Portable (10 kg) Small size (7.5 kg) allowing for portability
Requires separate monitoring console Able to monitor 2 circuit pressures simultaneously Continuous monitoring of multiple circuit pressures simultaneously
Streamlined console with simple display
Portable (15 kg)
Can exchange individual circuit components
Can exchange individual circuit components Less portable: requires back up console at all times (5.9 kg per console)
Pulmonary hypertension: pumpless drainage from pulmonary artery and reinfusion into left atrium to decompress right ventricle
Continuous monitoring of mixed venous oxygen saturation, hematocrit, and temperature
Can exchange individual circuit components
Full oxygenation/circulatory support: pump required. Diagonal flow pump can provide pulsatile flow
Cannot exchange individual circuit components and must change entire integrated setup
Portable (12 kg)
Can exchange individual circuit components
Continuous monitoring of multiple circuit pressures
Abbreviations: ECMO, extracorporeal membrane oxygenation; LPM, liters per minute; PECLA, pumpless extracorporeal lung assist (PECLA); RPM, revolutions per minute; VA, venoarterial; VV, venovenous.

ECMO circuits can be modified to allow insertion of a hemoconcentrator or continuous renal replacement therapy (CRRT) circuit. A hemoconcentrator is inserted distal to the blood pump so that it creates a convective force across the filter. Blood is then returned preblood pump. CRRT drainage and return lines can both be attached postblood pump and preoxygenator (Figure 6). In some centers, intravenous fluids and blood transfusions are given directly into the ECMO circuit, and this is typically done on the negative pressure (preblood pump) side of the circuit. Careful attention must be paid to deairing when giving intravenous fluids or blood transfusions preblood pump because massive air entrainment can occur with negative pressure. Most oxygenators have an arterial filter that removes particles larger than 40 µm, but large amounts of entrained air can cause an air lock, reducing or even stopping ECMO circuit blood flow. If connections are made to the circuit postblood pump, bleeding can occur if the connection is loose. For these reasons, the ECMO circuit should only be accessed by practitioners who have a high level of comfort and experience with the process.

Consensus Statement

Different ECMO centers have different levels of comfort and experience with infusing intravenous fluids and allogeneic blood products directly into the ECMO circuit and connecting other devices such as CRRT circuits. Attaching devices to or administering blood products or intravenous fluids directly into the ECMO circuit poses significant risks and should be performed only by experienced personnel with all connections carefully inspected before use. A major risk when accessing the negative pressure side of the ECMO circuit (preblood pump) is air entrainment. When the positive pressure side of the ECMO circuit (postblood pump) is accessed, there is a risk of bleeding if the connection is not secure.

ECMO BLOOD PUMPS, OXYGENATORS, AND CANNULAS

ECMO Blood Pumps

Modern ECMO blood pumps use centrifugal flow, where an impeller draws blood into a central inlet and propels it through an outflow orifice. This generates a continuous blood flow from the pump that is dependent on the pump’s revolutions per minute (RPMs), the patient’s volume status (preload), and resistance in the vessel where the blood is returned (afterload). The blood flow that can be achieved with contemporary centrifugal pumps is between 5 and 10 liters per minute, but actual blood flows in ECMO patients are almost never in the 7- to 10-liter per minute range because of resistance generated by the ECMO cannulas. Favorable characteristics of centrifugal pumps include fewer zones of blood stagnation and lower heat production, which reduces hemolysis.52,53 Centrifugal blood pumps that are approved by the United States Food and Drug administration include Rotaflow RF-32 (Getinge Group), Xenios DP3 (Xenios AG), Cardiohelp heart-lung support (HLS) 5.0 and 7.0 (Getinge Group), Quantum (CP37; Spectrum Medical), Revolution (LivaNova PLC), LifeSPARC (TandemLife), and CentriMag acute circulatory support system (Abbot). Table 3 lists characteristics of different centrifugal blood pumps.

Oxygenators

Modern oxygenators use a hollow fiber polymethylpentene frame where blood flows outside of the oxygenator’s fibers and oxygen flows within the fibers.54 Gas flow is referred to as “sweep” to distinguish it from blood flow and is responsible for providing oxygen to and removing carbon dioxide from the blood that passes through the oxygenator. Polymethylpentene is superior to silicone as an oxygenator material in terms of gas exchange and reduced coagulation system activation.55 OXYPLUS (3M), 3M Membrana (3M), and OXYPHAN (3M) are examples of polymers that are used in modern oxygenators.56 These materials have a sponge-like structure with irregular porosity. This structure limits the escape of blood and blood components into the membrane’s fibers and allows for efficient gas exchange.

Two types of oxygenators are used in adults: barrel shaped oxygenators, such as the Novalung XLung (Xenios AG), and polygonal oxygenators, such as the Quadrox-i (Gentinge Group; Figure 7). Barrel-shaped oxygenators have fewer areas of blood stagnation, which is an advantage. Polygonal oxygenators develop stagnant blood flow at their edges, which is the most common location for fibrin stranding to occur.57 Up to 40% of polygonal oxygenators have evidence of thrombosis after use, with the most common location being the apical corner.57 The surface area of an adult ECMO oxygenator is between 1.8 and 2.5 m2, depending on the manufacturer. Some manufacturers make “small adult” oxygenators such as the Quadrox-i for small adults (Gentinge Group) which has a lower priming volume, lower pressure drop, and lower surface area compared to a normal adult oxygenator. A small adult oxygenator should be used for patients who require <5 liters per minute of ECMO circuit blood flow.

F7
Figure 7.:
Figure shows two types of ECMO oxygenators. A, Barrel-shaped oxygenator and (B) polygonal oxygenator.

Sweep gas in the oxygenator flows perpendicular or countercurrent to blood flow. For example, in the Quadrox-i (Gentinge Group) sweep gas flows perpendicular to blood in 2 different directions.56 Carbon dioxide removal is directly proportional to the sweep gas-ECMO circuit blood flow ratio and varies between 100 and 350 mL per minute. To increase carbon dioxide removal, sweep gas flow is incrementally increased by 0.5 to 1 liter per minute for a given ECMO circuit blood flow. As the sweep gas-ECMO circuit blood flow ratio increases, the amount of carbon dioxide removed also increases. All modern oxygenators can provide heat exchange. Heat exchange occurs by conduction, with warm water circulated through the oxygenator housing to heat the blood.

Cannula Nomenclature and Design

The most common nomenclature used for ECMO cannulas refers to the cannula that drains venous blood from the patient as the “inflow” cannula, and the cannula that returns blood to the patient as the “outflow” cannula. The terms “drainage” and “return” cannula are also used and may be more intuitive.

Modern ECMO cannulas are made from polyurethane and are lined with biocompatible hydrophilic coatings, which contain covalently bonded heparin, albumin, or sulfate.58 Examples of biocompatible coatings include Bioline (Getinge Group), Smart-X (Sorin), and Trilium (Medtronic). The purpose of these coatings is to limit protein adsorption and coagulation system activation when blood comes into contact with artificial hydrophobic surfaces, such as circuit tubing.59

VA ECMO Cannulas

VA ECMO cannulas should be able to support ECMO circuit blood flow equivalent to a cardiac index of 2.2 to 2.5 L/m2/min. Cannula selection depends on the patient’s vessel size, target ECMO circuit blood flow, and anticipated level of physical activity during ECMO. In cases of emergent cannulation, smaller arterial cannulas may be used to facilitate rapid cannulation. Multistage (multiple sets of holes) venous drainage cannula sizes range from 21 to 29Fr, and the most common sizes used in adults are 23 and 25Fr. Return cannula sizes range from 15 to 21Fr. In one study, 15Fr arterial cannulas were found to be adequate for most VA ECMO patients, and smaller cannulas have the benefit of reduced vascular injury.60 Larger arterial return cannulas increase the risk for leg ischemia.61 When peripheral VA ECMO is performed, a distal perfusion cannula is used to provide distal leg perfusion. Distal perfusion cannula sizes range from 5 to 9Fr, and some centers use reinforced cannulas to prevent kinking. Use of smaller cannulas, 5 to 7Fr is preferable because it reduces the incidence of lower extremity ischemia. When small distal perfusion cannulas (eg, 5Fr) are used, the rate of lower extremity ischemia is <1%.62

VV ECMO Cannulas

Cannula selection for VV ECMO depends on the patient’s vessel size, target ECMO circuit blood flow, and anticipated level of physical activity during ECMO. ECMO circuit blood flow is limited by the size of the venous drainage cannula, rather than the return cannula.63 For average sized adults, VV ECMO cannulas should be able to support ECMO circuit blood flow of 50 to 80 mL/kg/min so that it can closely match intrinsic cardiac output.64 In morbidly obese patients, these flows are nearly impossible to achieve, and the goal should be to provide adequate ECMO circuit blood flow based on the patient’s condition, rather than a prespecified target. Single lumen, multistage venous drainage cannulas range in size from 21 to 29Fr and are like those used for VA ECMO. Return cannula sizes range from 17 to 25Fr.

Dual lumen VV ECMO cannulas range in size from 27 to 32Fr, depending on the manufacturer. Commercially available dual lumen VV ECMO cannulas include the Avalon Elite bicaval dual lumen cannula (Getinge Group), Crescent jugular dual lumen cannula (mc3corp), and OriGen reinforced dual lumen cannula (OriGen). Large dual lumen cannulas are associated with higher rates of intracranial hemorrhage, presumably from increased venous pressure in the brain, and there may be little benefit in terms of additional ECMO circuit blood flow or oxygenation.65 In general, it is prudent to use the smallest dual lumen VV ECMO cannula that allows for target ECMO circuit blood flow.

CANNULATION SCHEMES

Central and Peripheral VA ECMO

VA ECMO can be performed centrally or peripherally. In central VA ECMO, return blood from the ECMO circuit flows antegrade through the aortic arch and into the descending thoracic aorta. In peripheral VA ECMO, return blood flows retrograde up the descending thoracic aorta, where it mixes with blood that is ejected from the heart. The goals of VA ECMO are to increase effective cardiac output (ECMO circuit blood flow + intrinsic cardiac output), restore organ perfusion, and provide myocardial rest by reducing cardiac preload. Aortic valve opening and arterial pulsatility should be maintained with both central and peripheral VA ECMO to prevent intracardiac thrombosis and left ventricular distention. The decision about whether to use central or peripheral VA ECMO is based on accessibility of peripheral arteries, the scenario during which cannulation is performed, and the preferences of the cannulating physician.

Central cannulation has hemodynamic advantages but requires a sternotomy, and the sternum is generally left open, unless grafts or cannulas are tunneled through the chest wall. Its principal advantage is improved cardiac drainage, which reduces left ventricular distention and oxygen consumption to a greater degree.66 Central VA ECMO allows for higher ECMO circuit blood flow, which may be advantageous in patients with a high body surface area. Central VA ECMO is typically performed using a multistage venous drainage cannula inserted into the right atrium and an arterial cannula inserted into the ascending thoracic aorta (Figure 8).

F8
Figure 8.:
Central VA ECMO cannulation scheme with a multistage venous drainage cannula inserted into the right atrial appendage and an arterial cannula inserted into the ascending thoracic aorta. ECMO indicates extracorporeal membrane oxygenation; VA, venoarterial.

Peripheral cannulation has advantages that include cannulation ease, reduced sedation requirements, and lower risk for intrathoracic infection.67 Peripheral VA ECMO is most commonly performed using the left or right common femoral vein and the left or right common femoral artery with a distal perfusion cannula inserted into the ipsilateral superficial femoral artery (Figure 9). Peripheral VA ECMO can also be performed using the axillary or subclavian artery, and use of these vessels facilitates ambulation and reduces the risk of lower extremity ischemia. Axillary and subclavian artery cannulation are rarely performed during an emergency because most surgeons prefer to gain access to these arteries via surgical cutdown. Use of the axillary or subclavian artery can cause arm hyperperfusion, which occurs in up to 25% of patients and can lead to compartment syndrome or even limb loss in some cases.68 The rate of critical lower extremity ischemia with femoral artery cannulation is approximately 7% but can be reduced to 0% to 3% with distal leg perfusion.62,69

F9
Figure 9.:
Peripheral VA ECMO cannulation scheme with the arterial cannula passing into the left common femoral artery and a distal perfusion cannula passing into the left superficial femoral artery. ECMO indicates extracorporeal membrane oxygenation; VA, venoarterial.

Differential hypoxemia is a phenomenon that is unique to peripheral VA ECMO performed with femoral arterial cannulation. It occurs when deoxygenated blood that is ejected from the left heart mixes with oxygenated blood that is returned from the arterial cannula into the descending thoracic aorta.67 The exact mixing point of blood in the descending thoracic aorta depends on the patient’s intrinsic cardiac output, the amount of ECMO circuit blood flow, and the location of the arterial cannula tip. Differential hypoxemia can cause myocardial or cerebral hypoxemia when deoxygenated blood that is ejected from the heart perfuses the aortic root or aortic arch.

Peripheral VA ECMO generally provides comparable cerebral perfusion when compared to central VA ECMO and is not associated with a higher ischemic stroke risk.70 In rare cases, peripheral VA ECMO cannulation has been associated with ischemic spinal cord injury, but the mechanism by which this occurs is not fully understood.71–73

Dual Cannulation VV ECMO

Dual cannulation VV ECMO is most commonly performed using the left or right common femoral vein for the venous drainage cannula and using the right internal jugular vein for the return cannula. With this configuration, blood is drained out of the inferior vena cava (IVC), passes through the ECMO circuit where gas exchange occurs, and is returned into the internal jugular vein. When this configuration is properly set up, there should be minimal recirculation of blood, meaning that returned blood should not be drawn back into the drainage cannula. Use of the left or right common femoral vein and the right internal jugular vein has advantages that include minimal recirculation, superior oxygenation, and ease of conversion to VA ECMO when necessary.74 When correctly placed, the venous cannula tips should be located at their respective atriocaval junctions. In patients where ECMO support is adequate, the exact cannula tip location is not critical, and cannulas should not be adjusted solely based on their anatomic location. Patients with common femoral vein-right internal jugular vein cannulation can reliably participate in physical therapy.75

F10
Figure 10.:
A, Transesophageal echocardiography midesophageal bicaval view showing a correctly positioned dual lumen VV ECMO cannula in the SVC and IVC and (B) midesophageal bicaval view with color flow Doppler showing return blood flow correctly directed toward the tricuspid valve. ECMO indicates extracorporeal membrane oxygenation; IVC, inferior vena cava; LA, left atrium; LV, left ventricle; RA, right atrium; SVC, superior vena cava; TV, tricuspid valve; VV, venovenous.
F11
Figure 11.:
Transesophageal echocardiography modified midesophageal aortic valve short axis view. The VV ECMO cannula (ProtekDuo, Tandem Life) is seen directing return blood toward the main pulmonary artery. The tip of the cannula is approximately 4.3 cm past the pulmonic valve. ECMO indicates extracorporeal membrane oxygenation; MPA, main pulmonary artery; VV, venovenous.

Bifemoral cannulation is used less commonly for dual cannulation VV ECMO but may be necessary in cases where the internal jugular veins are not accessible (eg, face or neck trauma). When bifemoral cannulation is performed, the drainage cannula tip should be near the IVC-right atrial junction, and the return cannula tip should be positioned approximately 8 cm above to reduce recirculation.76 Disadvantages of bifemoral cannulation include increased infection risk, increased recirculation, and the potential for bilateral lower extremity deep venous thrombosis, which increases the risk of pulmonary embolism.

Single Cannulation VV ECMO

Dual lumen VV ECMO cannulas were designed to facilitate ambulation and reduce the number of access sites needed for VV ECMO.77 As previously described, there are multiple commercially available dual lumen cannulas. Disadvantages of dual lumen cannulas are their large size, which may increase the risk of vascular complications, and the need for echocardiography or fluoroscopy to guide insertion, confirm correct cannula position, and reduce the risk of right ventricle perforation.78–80 Dual lumen cannulas are placed via the right internal jugular vein in most cases. Use of the left internal jugular vein or subclavian veins is possible; however, it is more technically challenging.81,82 When a dual lumen cannula is in correct position, ECMO return blood flow should be directed toward the tricuspid valve (Figure 10).83,84 If ECMO return blood flow is not properly directed, it can cause increased recirculation and impaired oxygenation. The Protek Duo (Tandem Life) is a novel dual lumen VV ECMO cannula that provides right ventricular support. When properly positioned, its drainage orifices are in the right atrium and outflow orifices are located in the main pulmonary artery (Figure 11).85

Venoarteriovenous Extracorporeal Membrane Oxygenation

Venoarteriovenous (V-AV) ECMO provides both respiratory and biventricular circulatory support. In V-AV ECMO, there is drainage of blood from the central venous system, typically via the right or left common femoral vein, and blood is returned into a central vein (eg, internal jugular vein or common femoral vein) and peripheral artery (eg, left or right common femoral artery). V-AV ECMO is used to support patients with cardiogenic shock who have acute respiratory failure or patients with acute respiratory failure who have hemodynamic instability that does not improve after VV ECMO initiation.

ANTICOAGULATION

Changes in Blood Coagulation During ECMO

Patients on ECMO have changes in blood coagulation that include loss of large von Willebrand Factor (VWF) multimers, increased factor VIII activity, and reduced platelet surface glycoprotein (GP) 1bα density.86–89 Some changes promote hypercoagulability, whereas others contribute to increased bleeding risk. Enzymatic coagulation factors are skewed toward a procoagulant state in most ECMO patients with procoagulant factors increasing more than anticoagulant factors during the first few ECMO days as shock resolves.86 There are exceptions including patients who have progressive liver failure, patients with factor consumption from major bleeding, and patients who are post cardiotomy. Factor VIII is released from endothelial cells during ECMO and reaches >300% activity in many patients, leading to a supranormal underlying thrombin generation pattern when anticoagulation is held.86 For this reason, ECMO patients are prone to thrombosis, particularly in the setting of blood stasis.

Anticoagulant Drugs for ECMO

Given the procoagulant changes that occur during ECMO, systemic anticoagulation is administered whenever feasible. Systemic anticoagulation helps maintain circuit integrity, oxygenator function, and reduces the risk of stroke with central VA ECMO. Even with systemic anticoagulation, thrombosis occurs in 15% to 20% of ECMO patients.90,91 Fibrin stranding on the oxygenator and pump can cause hemolysis and worsen anemia. Severe hemolysis, which occurs in around 5% of ECMO patients, can be diagnosed by a plasma-free hemoglobin concentration >500 mg/L.92

There is a trend toward using less anticoagulation in ECMO patients and some ECMO centers have eliminated routine systemic anticoagulation.93–95 Although systemic anticoagulation can be safely held in many patients for days, as long as adequate ECMO circuit blood flow is maintained, witholding anticoagulation is associated with a circuit thrombosis rate of 35%.96 ELSO continues to recommend the use of systemic anticoagulation in patients who do not have major bleeding or a high bleeding risk.97

The gold standard for systemic anticoagulation is intravenous unfractionated heparin, which is widely available, inexpensive, and reversible. Direct thrombin inhibitors are also used for anticoagulation during ECMO, but there are no randomized studies to support their superiority over heparin, and they are generally more expensive. Bivalirudin’s half-life is prolonged when glomerular filtration rate falls below 30 mL per minute, and argatroban’s half-life is prolonged in cases of acute or chronic hepatic dysfunction. Table 4 lists important characteristics of commonly used anticoagulants.

Table 4. - Anticoagulation for ECMO
Anticoagulant Mechanism of action Half-life Elimination route Typical infusion dose range described in literature Typical therapeutic target described in the literature Advantages Disadvantages
Unfractionated heparin Enhances antithrombin activity against FXa and FIIa, inhibits only circulating thrombin 30 min–2 h Uptake into hepatocytes and reticuloendothelial cells 10–20 U/kg/h aPTT Half-life of larger heparin molecules not affected much by renal failure LMWH molecules have longer half-life with significant renal impairment
 VV: 40–60 s
 VA: 60–80 s
ACT
Inexpensive and widely available Occurrence of HIT in approximately 1%–5% of patients
 VV: 140–180 s
 VA: 180–220 s
Also inhibits activation of FXIII
Anti-Xa Dependent on adequate antithrombin activity (typically needs to be >80%)
 VV: 0.3–0.5 IU/mL
 VA: 0.5–0.7 IU/mL
Affected by recent drug shortages related to swine infections
Bivalirudin Reversible direct thrombin inhibitor, inhibits both circulating thrombin and fibrin bound thrombin GFR ≥90 mL/min: 25 min Enzymatic cleavage in plasma and renal elimination 0.05–0.5 mg/kg/h aPTT Short half-life Increases both aPTT and INR
 VV: 40–60 s No concerns about HIT
 VA: 60–80 s Half-life prolonged by 80% in patients on RRT
GFR = 60–89 mL/min: 22 min ACT No concerns about antithrombin deficiency
 VV: 140–180 s
 VA: 180–220 s High cost compared to heparin
GFR = 30–59 mL/min: 34 min Greater consistency in reaching target anticoagulation range
GFR = 10–29 mL/min: 57 min
No dose adjustment needed for hepatic dysfunction
Dialysis dependent: 3.5 h
Argatroban Reversible direct thrombin inhibitor, inhibits both circulating and fibrin bound thrombin 39–51 min Metabolized in liver by cytochrome P450 enzymes and primarily excreted in bile 0.2–1.0 µg/kg/min aPTT Relatively short half-life Increases both aPTT and INR
In patients with Child-Pugh >6, half-life is prolonged to 181 min  VV: 40–60 s
 VA: 60–80 s No concerns about HIT Half-life prolonged significantly in patients with acute and chronic liver disease
ACT
No concerns about antithrombin deficiency
 VV: 140–180 s
 VA: 180–220 s
High cost compared to heparin
Greater consistency in reaching target anticoagulation range
No dose adjustment needed for renal dysfunction
Abbreviations: ACT, activated clotting time; aPTT, activated partial thromboplastin time; ECMO, extracorporeal membrane oxygenation; GFR, glomerular filtration rate; HIT, heparin-induced thrombocytopenia; INR, international normalized ratio; LMWH, low molecular weight heparin; RRT, renal replacement therapy; VA, venoarterial; VV, venovenous.

Argatroban and bivalirudin are used to treat ECMO patients with suspected or confirmed heparin-induced thrombocytopenia (HIT). HIT risk stratification during ECMO should be performed using the 4T score, which includes 4 variables (thrombocytopenia magnitude, timing of platelet fall, thrombosis, and other causes of thrombocytopenia).98 The negative predictive value of a low 4T score exceeds 99% in non-ECMO patients and is similar in ECMO patients.98,99 When the 4T score is moderate or high, HIT diagnostic testing should be performed using a sequential approach. First, antiplatelet factor-4 antibodies should be measured using an enzyme linked immunsorbent assay. If optical density exceeds the laboratory threshold for confirmatory testing, a functional assay such as the serotonin release assay or heparin-induced platelet aggregation assay is performed. Optical density cutoffs for confirmatory testing differ by laboratory, but the likelihood of HIT is very low if optical density is <1.0.100 Heparin-coated tubing and cannulas should be avoided in patients with suspected or confirmed HIT.

Consensus Statements

  1. Systemic anticoagulation with intravenous unfractionated heparin or a direct thrombin inhibitor (bivalirudin or argatroban) should be administered to ECMO patients who do not have active bleeding and are not deemed to be at high risk for bleeding. Administration of systemic anticoagulation lowers the risk of thromboembolism and increases circuit durability. There are currently no randomized controlled trials to support the superiority of a particular anticoagulant. Heparin remains the preferred drug for most patients because of its low cost and rapid reversibility. However, heparin’s efficacy is reduced in patients with antithrombin (AT) deficiency (AT <80%).
  2. Patients who have moderate or high probability for heparin-HIT based on the 4T score should have heparin held and should be started on a direct thrombin inhibitor if they do not have active bleeding or high bleeding risk.

Anticoagulation Monitoring

Three tests are used for heparin anticoagulation monitoring during ECMO: the activated partial thromboplastin time (aPTT), the activated clotting time (ACT), and the anti-Xa assay. The aPTT is a plasma-based assay where the patient’s plasma has phospholipid and an intrinsic pathway activator (eg, silica or ellagic acid) added and the time until a fibrin clot forms is recorded (normal range 30–40 seconds). The ACT is a whole blood assay where the patient’s blood has kaolin or celite added and the time until a clot forms is recorded (normal range 100–140 seconds, depending on the device).101 The anti-Xa assay is used to estimate plasma heparin concentration. To perform the assay, the patient’s plasma which contains heparin is mixed with a known amount of factor Xa and residual factor Xa activity is measured using a chromogenic substrate. Plasma heparin concentration is estimated from a standardized curve.

A recent multicenter international survey published in 2017 suggested that most ECMO centers use the ACT or aPTT for heparin anticoagulation monitoring, while 10% of centers use anti-Xa monitoring.102 At present, there are no randomized controlled trials comparing heparin monitoring strategies in adult ECMO patients. Each test has limitations, which must be considered when interpreting results. For example, the ACT is affected by platelet count and other intrinsic and common pathway factor deficiencies, whereas the aPTT is not impacted by platelet count.103 The anti-Xa assay has the benefit of not being affected by warfarin use, direct thrombin inhibitors, and antiplatelet drugs.104,105 The anti-Xa assay is affected by anti-Xa drugs like apixaban and rivaroxaban and this should be considered if these drugs were ingested within the prior 72 hours.

Target anticoagulation levels are variable in the published adult ECMO literature, which has made identification of an optimal anticoagulation target nearly impossible.102 Most centers use a “low intensity” protocol for VV ECMO and a “high intensity” protocol for VA ECMO, given the serious consequences of arterial thromboembolism. One systematic review that included over 600 patients from 18 studies suggested that there is a trade off with more bleeding and less thrombosis when an aPTT target above 60 seconds is used compared with a target below 60 seconds.106Table 4 lists common anticoagulation target ranges for the 3 tests.

Consensus Statements

  1. Heparin monitoring can be performed using the activated partial thromboplastin time, ACT, or anti-Xa assay. There are no randomized controlled studies to support the superiority of a particular monitoring strategy. Each center should use an assay that meets their needs. Important considerations include cost, assay turn-around time, and availability of trained personnel to run the test.
  2. Monitoring of direct thrombin inhibitors can be performed using the activated partial thromboplastin time or ACT. There are no randomized controlled studies to support the superiority of either strategy. Each center should use an assay that meets their needs. Important considerations include cost, assay turn-around time, and availability of trained personnel to run the test.

CONCLUSIONS

Anesthesiologists who manage ECMO patients in the operating room should have a solid understanding of the technical aspects of ECMO including ECMO circuit components, cannulation schemes, changes in blood coagulation that occur with extracorporeal circulation, and systemic anticoagulation that is given during ECMO. Understanding these concepts will allow for improved communication with members of the ECMO team and will facilitate troubleshooting when ECMO related problems arise during the intraoperative or immediate perioperative period.

ACKNOWLEDGMENTS

We thank the Society of Cardiovascular Anesthesiologists’ guideline committee and quality, safety, and leadership committee, especially Michael Boisen, MD, and Bruce Bollen, MD, for their help in preparing this expert consensus statement.

DISCLOSURES

Name: Michael A. Mazzeffi, MD, MPH, MSc, FASA.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

Name: Vidya K. Rao, MD.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

Name: Jeffrey Dodd-o, MD, PhD.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

Name: Jose Mauricio Del Rio, MD.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

Name: Antonio Hernandez, MD, MSc.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

Name: Mabel Chung, MD, MPH.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

Name: Amit Bardia, MD.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

Name: Rebecca M. Bauer, MD.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

Name: Joseph S. Meltzer, MD.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

Name: Sree Satyapriya, MD.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

Name: Raymond Rector, CCP.

Contribution: This author reviewed the literature and wrote and approved the final manuscript.

Name: James G. Ramsay, MD.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

Name: Jacob Gutsche, MD.

Contribution: This author conceived the consensus statement, reviewed the literature, and wrote and approved the final manuscript.

This manuscript was handled by: Nikolaos J. Skubas, MD, DSc, FACC, FASE.

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