Chapter 96: Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is a form of partial heart–lung bypass for patients with severe but potentially reversible respiratory and/or cardiac disease who have failed conventional therapies. There are 2 basic types of ECMO: venovenous (VV), which provides the support for the lung only, and venoarterial (VA), which provides support for both heart and lung. In both modalities, blood drained from the venous system is oxygenated outside the body. VA ECMO is similar to standard cardiopulmonary bypass in that both lungs and heart are bypassed. The purpose of ECMO is to allow time for intrinsic recovery of the lungs and/or the heart, also known as salvage therapy. It can also be used as a bridge to destination therapy such as patients waiting for heart/lung transplant or in certain instances as bridge to decision. During VV ECMO, gas exchange can be supported even in the absence of any pulmonary function but no direct cardiac support is provided. However, the cardiac functions often improve owing to increased oxygen delivery to the heart and concurrently reduced mechanical ventilation. In VA ECMO,

ECMO utilization in adults with respiratory failure dates back to 1970s. A multicenter trial evaluating prolonged venoarterial (VA) ECMO for patients with severe acute respiratory failure failed to show reduction in mortality (> 90% mortality in both groups).¹ The study was later criticized for several reasons such as premature closure, lack of established ECMO experience in some centers, exclusive use of VA ECMO, extensive blood loss during the procedure, and lack of “lung rest” ventilator settings among ECMO patients.² ECMO regained cautious attention in the 1990s after several trials showed successful application in neonates and children.^3,4,5 In an uncontrolled study by Gattinoni and colleagues, venovenous (VV) ECMO improved survival in patients with acute respiratory failure while keeping lungs “at rest” (actual mortality 51.2% vs expected mortality 90%).⁶ A subsequent uncontrolled study involving only 10 patients showed similar results but also emphasized that ECMO should be applied early in the course of the disease.⁷ In a series of subsequent publications by Bartlett and colleagues showed that ECMO is a successful therapeutic option in patients with severe ARDS who do not respond to conventional mechanical ventilator strategy with survival in such patients in excess of 50%.^8,9,10 H1N1 influenza emerged as a major cause of respiratory failure during the 2009 epidemic. Favorable outcomes were reported with ECMO use in several studies with survival approaching 80% in patients who were otherwise not responsive to conventional treatment.^11,12 In a multicenter randomized controlled trial published in 2009, ECMO showed a survival benefit at 6 months.¹³ Nonetheless, results of this trial need to be interpreted with caution as all patients with ECMO were treated at a different center whereas control patients remained at referring center. More recent meta-analysis published in 2013 concluded that benefit of ECMO on hospital mortality is unclear.¹⁴ Currently, a multicenter randomized trial is underway, evaluating the impact of ECMO instituted early after the diagnosis of ARDS that is not evolving favorably after 3 to 6 hours of maximum medical treatment. (clinicaltrials.gov identifier: NCT014470703).

Clinical Use

ECMO should be considered in patients with life threatening but potentially reversible cardiorespiratory failure who do not have contraindications to extracorporeal support.

Indications

1. Respiratory indications:

   1. Inability to ventilate or oxygenate patients in situations where reversal of underlying condition is expected. Some examples include:

      • Pneumonia

      • Pulmonary embolism

      • Adult respiratory distress syndrome

      • Asthma/COPD exacerbation

      • Aspiration pneumonitis

      • Near drowning

      • Wegener granulomatosis

      • Acute chest syndrome, etc

      • Lung transplantation (graft failure)

   2. Bridge to lung transplantation

2. Cardiac indications:

   1. Patients with cardiogenic shock as manifested by inadequate tissue perfusion, hypotension and low cardiac output. Typical etiologies include:

      • Acute myocardial infarction

      • Decompensated heart failure

      • Peripartum cardiomyopathy

      • Fulminant myocarditis

      • Heart transplantation (graft failure)

      • Right heart failure

   2. Bridge to heart or heart–lung transplant

   3. During cardiac procedures such as:

      • CABG

      • Aortic valve replacement

Contraindications

ECMO should not be considered for irreversible or non-acute illnesses. Some relative contraindications include:

• Contraindication to anticoagulation

• Preexisting medical conditions affecting quality of life such as advanced malignancies, advanced malignancies

• Multiorgan failure

• End-stage organ failure in a patient not a candidate for destination therapy (ECMO is never used as a destination therapy)

• Medical futility

• VV ECMO: In VV ECMO, deoxygenated blood is drained from the cannula placed in large central vein, typically inferior vena cava (IVC), and oxygenated blood is returned through a cannula with its tip lying in or at a close proximity to the right atrium (RA). This oxygenated blood mixes with deoxygenated blood from patient’s systemic venous return and therefore it is not possible to obtain normal arterial oxygen saturation especially if the lungs are not contributing to the oxygenation. Usual target for oxygen saturation in a patient on ECMO circuit is 86% to 92%. Ideally, the blood from the return cannula passes through the tricuspid valve and then into pulmonary circulation thereby avoiding recirculation through the ECMO circuit. Pulmonary arterial blood is a combination of systemic venous return and oxygenated blood from the return cannula. Preoxygenator oxygen saturation is often used as a surrogate for systemic venous oxygen saturation. As there is always some recirculation present, the preoxygenator oxygen saturation is higher than the venous oxygen saturation. Depending on the positions of cannula, a variable proportion of oxygenated blood from the return cannula enters the drainage cannula, called recirculation. Recirculation reduces the delivery of oxygenated blood into the pulmonary circulation. Recirculation is influenced by several factors such as position of the drainage and return cannula, ECMO circuit flow, intravascular volume status, cardiac output, and position of the patient. High preoxygenator saturation in combination with low systemic arterial saturation suggests clinically significant recirculation. Conversely, low pre-oxygenator saturation along with low arterial saturation suggests that either the cardiac output is abnormally high or ECMO flow is low. High difference between the 2 variables usually suggests minimal recirculation. In the absence of an abnormally high cardiac output or hypermetabolic state, arterial oxygen saturation above 85% can be achieved with VV ECMO even in the absence of pulmonary function.

• VA ECMO: In VA ECMO, systemic venous blood drains into the circuit via a cannula placed in vena cava. This blood then passes through the pump and the oxygenator/heat exchanger prior to returning to the patient via a cannula placed in a large artery. This mode works on similar principals to cardiopulmonary bypass in that both heart and lungs are bypassed. Blood is returned to the arterial system and systemic arterial blood pressure is the sum of the ECMO circuit flow plus any ejection from the left ventricle. Likewise, systemic blood pressure is determined by the total blood flow and intrinsic arterial tone. Flow and FiO₂ of the sweep gas which controls the gas exchange by the oxygenator, it is usually the FiO₂ that determines oxygen tension and the flow which determines carbon dioxide tension. In the absence of LV function, the patient’s systemic oxygenation depends on the oxygenation in the circuit. However, if there is LV function, the systemic oxygen saturation will depend upon the flow through the ECMO circuit and the amount of blood ejected by the LV. In situations where lung function is severely impaired, placing the return cannula in femoral circulation can lead to upper body hypoxemia as the proximal branches of aorta receive predominantly deoxygenated blood ejected from the LV. Arterial CO₂ tension is determined by balance between carbon dioxide production and its elimination (from the lung or by the oxygenator). It can usually be easily controlled by adjusting flow through the circuit even if the lung is severely damaged.

An ECMO circuit consists of (1) a drainage and return cannula, (2) a oxygenator/heat exchanger, (3) a blood pump, and (4) a tubing. Except for differences in the cannula, identical circuits are used for both VV and VA ECMO.

• Oxygenator: Membrane oxygenators can be classified by their structure as either hollow fiber or flat sheet and by their membrane as either microporous or nonmicroporous. Microporous have large number of tiny holes through which gas exchange takes place where in nonmicroporous membrane oxygenators, gas exchanges occurs through diffusion. A decade ago, most of the adult ECMO was performed by using silicone membrane oxygenators that contain nonmicroporous membrane in a rolled flat sheet construction. While having excellent biocompatibility and durability, compared to hollow fiber oxygenators, provided less efficient gas exchange and were more bulky with higher resistance and difficult to prime. Polyprophylene hollow-fiber oxygenators are the standard oxygenators used during CPB. These microporous oxygenators while being highly efficient for gas exchange over short term, but over time the micropores become permeable to fluid causing plasma leaks into the gas phase and out the exhalation port. More recently a new generation of oxygenator containing nonmicroporous hollow fibers constructed of polymethylpentene (PMP) have been introduced. These oxygenators combine the durability of silicone membrane with ease of use and efficient gas exchange of hollow fiber construction. These oxygenators not only have improved durability, but also reduce the requirement of blood transfusion.

• Blood pump: There are two basic types of pump: (1) roller and (2) centrifugal. Roller pumps consist of flexible tubing in a curved raceway and are mounted on a rotating arm thus pushing the blood ahead. This pump is usually used with blood-filled bladder that is sited between drainage cannula and the pump to allow continuous pumping despite changes in intravascular volume. As the drainage into the bladder occurs via gravity, these pumps must be kept below the level of the patient. Roller pumps are usually afterload independent; thus, in the presence of obstruction distal to the pump, extremely high pressures can develop leading to circuit rupture. A centrifugal pump consists of a disposable pump head with magnetically driven impeller. The impeller spins rapidly, thus creating a pressure difference across the pump head that causes blood to flow. These are small, easy-to-prime pumps and have a very low volume. The blood flow is preload and afterload dependant such that there is no fixed relation between pump speed and blood flow. For the same reason, a large rise in blood pressure may reduce the blood flow and the pump failure during VA ECMO can even cause flow reversal. Hemolysis occurs with both roller and centrifugal pumps, although it is less with centrifugal pumps.

• Cannulae and tubing: Adequate size cannula is essential for adequate blood flow. For most adults, drainage cannula should be 23F to 25F and return cannula should be 17F to 21F. Tubing for the adult ECMO is 3/8 inch in diameter constructed of polyvinylchloride.

In most ECMO centers, perfusionists provide a primed, clamped ECMO circuit into the operative field. The circuit is usually primed with crystalloids, however, for anemic patients a blood prime can be used. It is important to correctly distinguish drainage cannula from return cannula. Both limbs of the circuit are clamped and the tubing is cut 10 cm distal to the clamp. Once connected, all clamps are released except for the clamp between the pump and the oxygenator. The pump is turned on to 1000 to 1500 rpm and the last clamp is slowly released. The sweep gas should initially be set at the same flow as ECMO circuit flow and then adjusted according to PaCO₂ and pH. It is common for patients to become hypotensive once ECMO is initiated and appropriate medications for its treatment should be available ahead of time. Patient is heparinized to achieve an activated coagulation time of 1.5 to 2.0 times the normal. Circuit flow is titrated to clinical parameters, which for VA ECMO are mean arterial pressure and arterial oxygen saturation, and, for VV ECMO are arterial oxygen saturation and oxygen saturation in the drainage cannula.

Once ECMO is established, ventilator is set to rest settings. Typical rest ventilator settings are pressure controlled ventilation with peak inflation pressure of 20 to 25 cm H₂O, positive end expiratory pressure of 10 to 15 cm H₂O, and a respiratory rate of 4 to 8 breaths/min. Patients typically develop systemic inflammatory response in the first few days as a consequence on ongoing critical illness and blood contact with ECMO circuit. This may lead to a vasodilator shock, worsening of acute lung injury, and third space fluid losses. If SaO₂ remains low despite adequate circuit flow or if the flow is low despite adequate pump speed, flow pattern in the cannula should be checked using color Doppler with transesophageal echocardiography to rule out any obstruction. The same technique can also be used to check reversibility in the flow. Several other aspects of care need to be managed alongside the ECMO while taking care of these patients. As ECMO support for respiratory failure may extend for weeks, patient may become tolerant to benzodiazepines and opioids. Similarly, weaning off the patients from these medications could be difficult after prolonged use. Thus, administration in low doses is recommended for these medications. Some centers even wake up and extubate some patients although this can be technically challenging. Anticoagulation with unfractionated heparin is required while patient is on ECMO circuit. Patients need to be monitored for the signs of bleeding which can result from anticoagulation, thrombocytopenia (heparin-induced, sepsis), disseminated intravascular coagulation or from gastrointestinal sources. Performing coagulation studies, monitoring the blood counts, and checking a thromboelastogram (TEG) will help in diagnosing the etiology in such circumstances. In certain instances, ECMO circuit can be run heparin free for around 48 to 72 hours.

Maintaining fluid balance is another important consideration in these patients as they often get flooded with volume during the initial resuscitation period. Thus, it is recommended to limit fluid administration and ideally maintain a negative balance even if it leads to use of vasopressors.

VV ECMO: Recovery of the pulmonary functions may take days to weeks. Signs such as improvement in oxygen saturation for a given circuit flow, progressive increase in SaO₂ above SvO₂, improving lung compliance and chest radiography. Once a patient is able to maintain a saturation of > 90% at a circuit flow of 1 to 2 L/min, weaning trial can be instituted. Circuit flow is progressively decreased while fully ventilating patient with the ventilator. Once flow is reduced to zero and patient is able to tolerate, ECMO is decannulated.

VA ECMO: Pulsatility is an early sign of recovery of myocardial function. Ionotropic support is started prior to planned weaning and circuit flow are slowly reduced to 1 to 2 L/min. Echocardiography is done during the process to assess cardiac function. Once patient is stable on minimal or no support, ECMO can be discontinued. Majority of the patients who are able to be weaned of VA ECMO do so within 2 to 5 days.¹⁵

Circuit Complications

ECMO is a complex procedure performed on critically ill patients, thus have high potential for complication.

Gas embolism:

Large negative pressure generated with the centrifugal pumps can lead to air entrainment and significant air embolism. A major obstruction in the circuit can also force the gas out solution causing gas embolism. This complication, though life threatening, is rare and occurs in fewer than 2% of adult ECMO runs.¹⁶

Blood clots: Blood clots can occur at multiple sites in the ECMO circuit. Clot in the pump head usually results in change in sound of the pump and rising plasma hemoglobin. A clot in the oxygenator can result in increasing pressure gradient along with fall in post oxygenator PO₂ and increasing sweep gas needed to maintain PaCO₂. Other markers such as increasing d-dimers or fibrin degradation products can also suggest clot formation.

Loss of circuit flow: Loss or reduced flow is most commonly caused by hypovolemia. Other causes such obstructive shock from cardiac tamponade or tension pneumothorax and malpositioned cannula can also decrease the flow. With a roller pump, a decreased flow can lead to slowing or stopping of the pump. In ECMO devices with a centrifugal pump, a decreased flow can lead to increased negative which can progress to suck down at the drainage cannula eventually causing loss of circuit flow.

Circuit failure or breakage: As the name sounds, this complication may lead to a catastrophic complication. Bedside staff trained to check circuit integrity and to react promptly in the case of acute failure can prevent this problem.

Patient Complications

Hemodynamic instability: Circuit flows above 7 L/min are rarely possible even with the optimal cannula. In patients on ECMO support, severe sepsis can lead to significant hypotension as it normally would lead to increase in cardiac output. Left ventricular (LV) distension can occur in patients on VA ECMO especially in patients with mitral or aortic regurgitation, which can lead to pulmonary edema. Increasing pump flow may be helpful in such situations.

Hypoxemia: Upper body hypoxemia can occur in VA ECMO patients with significant LV ejection and impaired lung function. This situation typically occurs when return cannula is placed in lower extremity arteries. Detecting higher saturation in lower extremity compared to upper extremity diagnosis this problem.

Infections: Infective complications related to access sites, indwelling lines or primary pathology can occur. Of note, signs of sepsis may be completely evident; in particular, fever may be absent due to control of temperature via heat exchanger. Thus, any evidence of deteriorating hemodynamics or rising white cell count should be taken seriously. Strict aseptic precautions need to be taken during this process.

Bleeding: Bleeding, in particular from the surgical site, is common during ECMO. In one series, approximately 31.4% patients developed cannulation site bleeding and 26.7% developed surgical site bleeding.¹⁷ Other less common but potentially more serious bleedings could be gastrointestinal and intracranial bleeding which were 7% and just fewer than 3% in same series respectively. Most important mechanism of dealing with this complication is prevention. All unnecessary procedures should be avoided as much as possible while patient is on ECMO.

VV ECMO may be used as an alternative to cardiopulmonary bypass during procedures involving airway and lungs. Examples include surgical construction of carina,¹⁸ laser resection of tracheal masses,¹⁹ whole lung lavage for alveolar proteinosis,²⁰ during high risk rigid bronchoscopy,²¹ and in adult burn patients with severe inhalational injury.²² Successful use of VA ECMO has been reported in several different clinical situations such as in patients with toxic shock-induced cardiomyopathy,²³ ARDS with septic cardiomyopathy,²⁴ to facilitate combined pneumonectomy and transesophageal fistula repair,²⁵ as a “bridge to bridge” in heart failure patients,²⁶ in patients with cardiac arrest,^27,28,29 and as a bridge to organ donation.³⁰ These examples show that ECMO can be used successfully to support vital organ perfusion in patients with profound but potentially reversible medical conditions.

ECMO is highly technical, advanced life support system used for patients with severe cardiac and or pulmonary disease requiring intensive support with a potential for reversibility. With improvements in ECMO device and increasing ECMO experience, there is potential for further improvement in outcomes inpatient on this support. Some experts have started to suggest early implementation of ECMO as a part of lung protection in patients with ARDS.^31,32 ECMO is currently being offered in equipped centers for ARDS patients with severe hypoxemia (PaO₂-to-FiO₂ ratio < 80 mm Hg) who are unresponsive to conventional treatment. The feasibility and efficacy of ECMO for in-hospital cardiac arrest patients have been reported.³³ However such efficacy and cost effectiveness for out-of-hospital cardiac arrest remain unclear and further studies are needed to assess this modality. Extracorporeal removal of CO₂, a function of ECMO circuit, can be potentially used in critically ill patients with acute exacerbation of bronchial asthma and COPD who are unable to tolerate standardized management, although definite guidelines are lacking. Safe application of this device would require multidisciplinary team approach, and experience with its use and improvements to minimize device related complication, before this modality can be applied across the board.