Venovenous Extracorporeal Membrane Oxygenation (VV-ECMO)

Modalities of Extracorporeal Life Support (ECLS)

  • Cardiopulmonary Bypass (CPB) (see Cardiopulmonary Bypass, [[Cardiopulmonary Bypass]])
  • Extracorporeal CO2 Removal (ECCO2R): originally developed by Gattinoni (JAMA, 1986) [MEDLINE]
  • Extracorporeal Membrane Oxygenation (ECMO)
    • Venovenous Extracorporeal Membrane Oxygenation (VV-ECMO)
    • Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) (Percutaneous Cardiopulmonary Support, CPS)

Differences Between Cardiopulmonary Bypass and Extracorporeal Membrane Oxygenation (ECMO) (see Cardiopulmonary Bypass, [[Cardiopulmonary Bypass]])

  • Cardiopulmonary Bypass is Equipped with Reservoir Into Which Blood from the Heart is Drained: allows a bloodless surgical field for valve and aortic operations
    • In Contrast, the ECMO Circuit Does Not Contain a Reservoir, So Blood Flow Needs to Be Continuous
  • Cardiopulmonary Bypass Can Be Utilized in Conjunction with Air Vent Tubing, Cardioplegia Line for Myocardial Preservation, or Cell Salvage Tubing
  • Requirement for Systemic Heparin Anticoagulation is Less Intense for ECMO Because Blood Flow is Continuous and There is No Blood-Air Interface in the Reservoir
    • Higher Flow Rates of >4 L/min are Used During ECMO (in Contrast to the Lower Flow Rates of 2 L/min Used During CPB)
    • However, Continuous Anticoagulation is Necessary to Prevent Thrombus Formation on the Synthetic Thrombogenic Surfaces of Both CPB and ECMO
  • ECMO Circuits are Designed for Longer-Term Use (May Be Used for Weeks, Depending on the Life of the Membrane Oxygenator), While CPB Use is Designed for Use for a Period of Hours

Indications

General Comments

  • Venovenous Extracorporeal Membrane Oxygenation (VV-ECMO) (Similar to Extracorporeal CO2 Removal, ECCO2R) Provides Only Respiratory Support: VV-ECMO is dependent on the patient’s intrinsic cardiac output

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])

Clinical Efficacy

  • Early JAMA ECMO Trial (JAMA, 1979) [MEDLINE]
    • ECMO Had No Mortality Benefit
  • ECCO2R Trial (Am J Respir Crit Care Med, 1994) [MEDLINE]
    • ECCO2R Had No Mortality Benefit
  • ANZ ECMO Influenza Trial (JAMA, 2009) [MEDLINE]
    • ECMO Had No Mortality Benefit in Treatment of ARDS Associated with Influenza
  • CESAR Trial of ECMO in the UK (Lancet, 2009) [MEDLINE]
    • ECMO Decreased Mortality Rate/Severe Disability at 6 Months
    • However, the Study was Flawed by Not Defining the Usual Care Group and ECMO Patients Were Concentrated in One Center in the Trial
  • Systematic Review and Meta-Analysis of ECMO in Adult Patients with ARDS ( J Crit Care. 2013) [MEDLINE]
    • ECMO Had an Unclear Hospital Mortality Benefit: further studies were recommended
  • Cochrane Review of VV-ECMO and VA-ECMO in Critically Ill Adults (Cochrane Database Syst Rev, 2015) [MEDLINE]
    • ECMO Had No 6-Month (or Prior to 6 Month) All-Cause Mortality Benefit: low-moderate quality of evidence from trials

Criteria to Start Venovenous Extracorporeal Membrane Oxygenation (VV-ECMO)

  • French REVA (Reseau Europeen De Recherche En Ventilation Artificielle) Criteria (2009)
    • pO2/FiO2 Ratio <50 Despite High PEEP (10-20 cm H2O) and High FiO2 (>80%)
    • Plateau Pressure At Least 35 cm H2O Despite Decrease in Tidal Volume to 4 mL/kg
  • NEJM, 2011 Review of ECMO in ARDS Criteria [MEDLINE]
    • Severe Hypoxemia: pO2/FiO2 Ratio <80 Despite High PEEP (15–20 cm of H2O) for at Least 6 hrs in Patient with Potentially Reversible Respiratory Failure
    • Uncompensated Hypercapnia with Acidemia (pH <7.15) Despite the Optimized Ventilator Management
    • Excessively High Plateau Pressure (>35–45 cm of H2O, According to the Patient’s Body Size) Despite Optimized Ventilator Management
  • Extracorporeal Life Support Organization (ELSO) Criteria
    • pO2/FiO2 Ratio <150: ECMO should be considered
    • pO2/FiO2 Ratio <80: ECMO should be utilized
    • pCO2 >80 m Hg or Plateau Pressure >30 cm H2O: ECMO should be utilized

Contraindications

Absolute

  • Contraindication to Anticoagulation: although in patients with severe bleeding, anticoagulation can be held for limited periods of time

Relative (NEJM, 2011) [MEDLINE]

  • Any Condition or Organ Dysfunction that Would Limit the Likelihood of Overall Benefit from ECMO, Such as Severe, Irreversible Brain Injury or Untreatable Metastatic Cancer
  • High FiO2 Requirement >80% for >7 Days
  • High-Pressure Ventilation (Plateau Pressure >30 cm of H2O) for >7 Days
  • Limited Vascular Access

Physiology

Major Determinants of Oxygenation During VV-ECMO

  • VV-ECMO Blood Flow Rate
  • VV-ECMO FIO2

Factors Contributing to Hypoxemia During VV-ECMO (Excluding Equipment Failure)

  • Mixture Between ECMO Oxygenated Blood and Patient’s Own Venous Blood
    • Mixing Occurs in the Right Atrium (Using the Avalon Catheter Inserted Via the Right Internal Jugular Vein)
    • Assuming No Gas Exchange is Occurring Across the Lung, This Implies that the SaO2 of the Blood in the Right Ventricle Equals the SaO2 on the Arterial Side of the Circulation
    • For This Reason, Extracorporeal Life Support Organization (ELSO) Guidelines Recommend Setting an ECMO Blood Flow Rate of Approximately 50-80 mL/kg/min [LINK]
      • This Will Guarantee an Oxygen Delivery (DO2) of 3 mL/kg/min and a Pump Flow/Deoxygenated Blood Ratio of 3:1
      • However, in Sepsis Where Cardiac Output is Typically Elevated, This 3:1 Ratio Can Only Be Maintained if Flow is Augmented
  • Recirculation: defined as the fraction of oxygenated blood which is infused into the right atrium and subsequently aspirated back into the venous limb of the ECMO circuit
    • Factors Contributing to Recirculation
      • Cannula Type/Size
      • Cannula Position
      • Pump Speed
      • Blood Flow Rate
      • Direction of Extracorporeal Blood Flow
      • Intrathoracic/Intracardiac/Intra-Abdominal Pressures
  • Intrapulmonary Shunt: this is the main mechanism of hypoxemia in ARDS (occurs due to alveolar filling with protein-rich fluid/red blood cells/neutrophils and interstitial changes)
    • Degree of Intrapulmonary Shunt is Related to Vascular Pressures, Vasoactive Medications/Substances, and Degree of Lung Inflation
    • Cardiac Output is Positively Correlated with the Degree of Intrapulmonary Shunt
  • Flow Exceeding Oxygenator Performance: rarely occurs with current generation of technology

Strategies to Improve Peripheral Oxygenation During VV-ECMO

  • Increase Blood Oxygen Content
    • Increase ECMO Blood Flow Rate
      • In Some Cases, Increasing the Blood Flow Rate Will Not Improve Oxygenation, Due to Increased Recirculation
      • Higher Flow Rates Increase the Risk of Hemolysis (see Hemolytic Anemia, [[Hemolytic Anemia]]): may occur when using high RPM with venous occlusion in the catheter (due to coughing, hypovolemia, catheter kinking, etc), resulting in a vacuum created in the pump head
    • Increase Hematocrit (Oxygen-Carrying Capacity)
      • ECMO Utilization is Blood Resource Intensive: due to the need for frequent PRBC transfusion related to both hemolysis/bleeding issues and the need to maintain a high hematocrit to increase oxygen delivery (DO2)
      • Extracorporeal Life Support Organization (ELSO) Guidelines Recommend Maintaining a Hemoglobin of 12-14 g/dL with a Normal Hematocrit (v1.3 (2013) [LINK]: due to the fact that oxygen delivery (DO2) is determined by blood flow through the artificial lung, and if anemic is present, a higher blood flow will be necessary to obtain the same level of oxygen delivery (DO2)
      • While There are No Trials Examining Restrictive Transfusion Protocols in VV-ECMO, Data Suggest that Red Blood Transfusion is a Clinical Predictor of Mortality (Crit Care Med, 2005) [MEDLINE] and (Chest, 2007) [MEDLINE]
  • Decrease ECMO Recirculation
    • Maximize the Distance Between the Two Cannulas
  • Decrease Oxygen Consumption
    • Sedation (see Sedation, [[Sedation]])
    • Neuromuscular Blockade (see Neuromuscular Junction Antagonists, [[Neuromuscular Junction Antagonists]])
    • Therapeutic Hypothermia (see Therapeutic Hypothermia, [[Therapeutic Hypothermia]])
      • Hypothermia Decreases the Metabolic Rate
      • Hypothermia Also Increases the Solubility of Oxygen in Blood
  • Manipulation of Cardiac Output and Intrapulmonary Shunt
    • Beta Blockers (see β-Adrenergic Receptor Antagonists, [[β-Adrenergic Receptor Antagonists]])
      • Esmolol Has Been Used to Decrease the Cardiac Output (in Patients with Cardiac Output >7 L/min), Improving the Ratio Between the Cardiac Output and the ECMO Blood Flow (Preventing the Need for Increases in the ECMO Blood Flow Rate): this treatment did not decrease the oxygen delivery (DO2)
        • Decreasing CO Also Decreases Intrapulmonary Shunt
    • Proning: while trials of combined proning and VV-ECMO have been performed, the efficacy of this strategy is unclear
  • Switch to Venoarterial ECMO (VA-ECMO) or Hybrid Configuration
    • Utilization of VA-ECMO Allows Complete Bypass of the Native Lung: allowing a strategy to manage refractory hypoxemia occurring during VV-ECMO
      • Arterial Catheterization Needs to Be as Close to the Heart as Possible to Avoid the “Harlequin Syndrome” (Blue Head and Red Legs): this occurs due to competition between the anterograde blood flow related to native cardiac output and ECMO flow delivered via a femoral cannula, resulting in compromised perfusion of the upper body

Technique

Equipment

  • Maquet Cardiohelp
    • Centrifugal Pump (Constrained Vortex Pump)
      • Centrifugal Pump Moves Blood by Creating a Pressure Differential Across the Pump Head Which Contains a Magnetically Driven Impeller Spinning at Approximately 3000 RPM
      • Centrifugal Pumps Require Lower Levels of Anticoagulation than Roller Pumps
      • Centrifugal Pumps Result in Lesser Degree of Hemolysis than Roller Pumps
      • Centrifugal Pumps Exhibit an Increased Risk of Non-Surgical (Gastrointestinal, Pulmonary, and Neurological) Bleeding, as Compared to Roller Pumps, Despite Lower Levels of Heparin Anticoagulation (ASAIO J, 2015) [MEDLINE]
    • Duration of Use: Maquet Cardiohelp may be used for up to 30 days (per manufacturer recommendation)

Vascular Access

  • Requirement for Technical Support: requires continuous monitoring by technical support personnel

Avalon Catheter Placement into the Right Internal Jugular (IJ) Vein (Avalon Laboratory, Los Angeles, CA, USA)

VV-ECMO

  • Required Supplies
    • Arrow Dilator Kit
    • Avalon Catheter
  • Insertion and Set-Up
    • Procure Right Internal Jugular (IJ) Access
    • Insert Long Stiff Wire
    • Serial Grey Dilators
    • Insert Black Wire Sheath Over Wire
    • Serial Dilation of Tract with Blue Dilators Over Wire/Sheath (Both Remain in Place During Dilation)
    • Insert Avalon Catheter Over Wire: orient arterial port toward patient chin (this angles the arterial port toward the tricuspid valve)
    • Remove White Stylet from Avalon Catheter
    • Use Trans-Esophageal Echocardiogram (TEE) to Assure that Arterial Port is Angled Toward the Tricuspid Valve
    • After Avalon Catheter Placement, Immediately Give Heparin 10,000 units IV: to prevent Avalon catheter from clotting
    • Fill Avalon Catheter Lines with Saline: squirt into ends of catheter just to fill
    • Connect Straight Venous Port (Green Arrow in Photograph) to ECMO Machine: unoxygenated blood should be seen in this line
    • Connect the Angled Arterial Port (Red Arrow in Photograph) to ECMO Machine: oxygenated blood should be seen in this line

Anticoagulation

  • Heparin Drip (see Heparin, [[Heparin]])
    • Titrate to Achieve ACT 220-260 sec
    • However, Anticoagulation May Be Held for Short Periods During EMCO (Using Heparin-Bonded Circuits)

Extracorporeal Life Support Organization (ELSO) Guidelines for Adult Respiratory Failure v1.3 (2013) [LINK]

  • Titrate Heparin Drip to Maintain ACT 180-200

Management (Extracorporeal Life Support Organization (ELSO) Guidelines for Adult Respiratory Failure v1.3, 2013) [LINK]

Adjustments To Increase the Arterial pO2

  • Increase ECMO Circuit Blood Flow Rate (Blue Arrow in Photograph): blood flow rate through exchanger
    • Start with 50-80 ml/dry weight/min (Approximately 3.5-5.6 L/min for a 70 kg Patient): this will achieve a DO2 of approximately 3 mL/kg/min (assuming a cardiac output of 5 L/min and hemoglobin concentration of 15 g/dL)
      • Start with the Maximum End of This Range Initially, Then Decrease to Lowest Blood Flow Rate to Maintain SaO2 >80-85% (at Resting Vent Settings)
        • Arterial pO2 Will Be 45-55 mm Hg in this Scenario: the lower limit of pO2 below which brain injury may occur during VV-ECMO is unknown (ASAIO J, 2015) [MEDLINE]
        • Note that the Compensatory Increase in Cardiac Output Which Occurs and Transfusion to Achieve a Hematocrit >40% Will Ensure Adequate Oxygen Delivery (DO2)
      • Goal DO2:VO2 Ratio >3 (Corresponds to an SvO2 Which is 25-30% Less than the SaO2)
        • Total DO2 = Patient Lung DO2 + Circuit DO2
        • Circuit DO2 = Flow x Outlet-Inlet O2 Content
        • VO2 = 3 ml/kg/min
    • The Ability to Achieve a Specific Blood Flow Rate Will Depend on the Vascular Access Characteristics, Drainage Tubing Resistance, and Pump Properties
      • Typical Pven (Venous Limb Pressure, Yellow Airway in Photograph) is Approximately -70 mm Hg (Example: -140 mm Hg Indicates an Excessively High Negative Pressure in Venous Limb of the Avalon Catheter, Which Might Prevent an Increase in the Blood Flow)
  • Increase Sweep Gas FIO2 (Red Arrow in Photograph)

Adjustments To Change the Arterial pCO2

  • Maintain Arterial pCO2 at 40 mm Hg by Altering the Sweep Gas Flow Rate (Green Arrow in Photograph): oxygen flow rate through exchanger (range: 1-10 L/min)
    • Increase in Sweep Gas Flow Rate Will Decrease the Arterial pCO2: functions similarly to the minute ventilation (VE) on the ventilator
    • Decrease in Sweep Gas Flow Rate Will Increase the Arterial pCO2: functions similarly to the minute ventilation (VE) on the ventilator
    • Sweep Gas Flow Rate is Usually 1:1 with the ECMO Blood Flow Rate
      • However, Sweep Gas Flow Rate Can Be Decreased to as Low as 1 L/min to Increase the Arterial pCO2
      • However, Sweep Gas Flow Rate Can Be Increased to as High as 10-15 L/min to Decrease the Arterial pCO2

Maintenance of a Near-Normal Hematocrit

  • Maintain Hemoglobin 12-14 g/dL (with a Normal Hematocrit)
    • Extracorporeal Life Support Organization (ELSO) Guidelines Recommend Maintaining a Hemoglobin of 12-14 g/dL with a Normal Hematocrit (v1.3 (2013) [LINK]: due to the fact that oxygen delivery (DO2) is determined by blood flow through the artificial lung, and if anemia is present, a higher blood flow will be necessary to obtain the same level of oxygen delivery (DO2)

Ventilator Management During Venovenous Extracorporeal Membrane Oxygenation (VV-ECMO)

  • Optimal Ventilator Management During ECMO is Unknown: rationale is to use adequate tidal volume to prevent lung atelectasis and use low respiratory rate to prevent ventilator-induced lung injury
  • Suggested Settings (Same as Used in the CESAR Trial): turn down vent settings gradually, while monitoring serial ABG’s
    • Pressure Control Ventilation (PCV) with RR 10, PIP 20-25 cm H2O (with Tidal Volume <4 mL/kg PBW), PEEP +10-15, and FiO2 30%

Addition of Prone Positioning to VV-ECMO Therapy

  • Clinical Efficacy
    • Systematic Review of Prone Positioning as Add-On Therapy to VV-ECMO (Respir Care. 2016) [MEDLINE]
      • Addition of Prone Positioning to VV-ECMO Had Unclear Benefit
      • Risk of Hemodynamic Instability and Catheter Dislodgment Were Low

Adverse Effects/Complications (NEJM, 2011) [MEDLINE]

  • Cannula-Related Problems: accounts for 8.4% of adverse events
  • Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation, [[Disseminated Intravascular Coagulation]]): accounts for 3.7% of adverse events
  • Hemolysis (see Hemolytic Anemia, [[Hemolytic Anemia]]): accounts for 6.9% of adverse events
    • Higher Flow Rates Increase the Risk of Hemolysis (see Hemolytic Anemia, [[Hemolytic Anemia]]): may occur when using high RPM with venous occlusion in the catheter (due to coughing, hypovolemia, catheter kinking, etc), resulting in a vacuum created in the pump head
  • Hemorrhage
    • Surgical Site: accounts for 19.0% of adverse events
    • Cannulation-Site Hemorrhage: accounts for 17.1% of adverse events
    • Pulmonary Hemorrhage (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]]): accounts for 8.1% of adverse events
    • Gastrointestinal Hemorrhage (see Gastrointestinal Hemorrhage, [[Gastrointestinal Hemorrhage]]): accounts for 5.1% of adverse events
    • Intracranial Hemorrhage: 3.8% of adverse events
  • Infection (Related to or Unrelated to ECMO): accounts for 21.3% of adverse events
  • Other Mechanical Complications: accounts for 7.9% of adverse events
  • Oxygenator Failure: accounts for 17.5% of adverse events
  • Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])
    • Epidemiology: common
    • Physiology
      • Heparin-Induced Thrombocytopenia (HIT) (see Heparin-Induced Thrombocytopenia, [[Heparin-Induced Thrombocytopenia]])
      • Platelet Consumption in ECMO Circuit: due to fibrin stranding in oxygenator
  • Thrombosis
    • Thrombosis in Oxygenator: accounts for 12.2% of adverse events
    • Thrombosis in Other Circuit: accounts for 17.8% of adverse events

References

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