Extracorporeal Membrane Oxygenation (ECMO)

Quick Answer

ECMO is extracorporeal circulatory support providing cardiopulmonary bypass when conventional therapy fails. VV-ECMO provides respiratory support (blood oxygenated, returned to venous system), VA-ECMO provides cardiac and respiratory support (oxygenated blood returned to arterial system).

Key thresholds: VV-ECMO for severe ARDS (P/F below 80 despite optimal ventilation, Murray score ≥3, pH below 7.25). VA-ECMO for refractory cardiogenic shock (CI below 2.0, lactate greater than 4, despite inotropes/pressors + IABP).

Complications: Bleeding (70%), thrombosis (10-20%), infection (30%), neurological injury (10-30%). Mortality: 40-60% overall, 30-50% VV-ECMO for ARDS, 50-70% VA-ECMO for cardiogenic shock.

Anticoagulation: Unfractionated heparin infusion targeting ACT 180-220s or anti-Xa 0.3-0.7 IU/mL. Heparin-bonded circuits allow reduced/no heparin in high bleeding risk.

Weaning: VV-ECMO - reduce sweep gas to maintain PaCO2 50-60 mmHg, reduce flow to 1.5-2 L/min, assess native lung function. VA-ECMO - reduce flow to 1-1.5 L/min, assess cardiac function with echo, bridge to VAD/transplant if recovery unlikely.

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CICM Second Part Exam Focus

Knowledge Domains

CICM Second Part candidates must demonstrate comprehensive understanding of:

• ECMO physiology: Oxygen delivery equation (DO2 = CO × CaO2), membrane oxygenator function, shunt fraction
• Indications and contraindications: Respiratory failure, cardiogenic shock, bridge to transplant/VAD, futility assessment
• Cannulation strategies: VV vs VA, cannula sizes, access sites (jugular, femoral, subclavian), Doppler-guided placement
• Circuit components: Pump (centrifugal), oxygenator, heat exchanger, cannulae, monitoring, alarms
• Management: Anticoagulation, ventilator settings, sedation, nutrition, haemodynamics, complications
• Weaning and decannulation: Criteria, protocols, success predictors, timing
• Evidence: EOLIA, CESAR, ELSO registry, survival data, quality of life outcomes

Common SAQ Themes

1. VV-ECMO for severe ARDS: Indications, timing, patient selection, management strategies
2. VA-ECMO for cardiogenic shock: Indications, cannulation strategies, venting, complications
3. ECMO complications: Bleeding, thrombosis, infection, limb ischaemia, neurological injury
4. ECMO weaning: Protocols, assessment criteria, success rates
5. ECMO in specific populations: Pregnancy, trauma, immunocompromised, elderly

Viva Themes

• ECMO indications: Patient selection, contraindications, futility
• Circuit physiology: Oxygenator function, haemodynamics, anticoagulation
• VV-ECMO vs VA-ECMO: Indications, cannulation, management differences
• Complications: Diagnosis, prevention, management
• Weaning: Assessment criteria, protocols, bridge to recovery/VAD/transplant

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Key Points

• VV-ECMO provides respiratory support only; VA-ECMO provides both cardiac and respiratory support
• VV-ECMO indication: Severe ARDS (P/F below 80 despite optimal ventilation for 6h, Murray ≥3, pH below 7.25)
• VA-ECMO indication: Refractory cardiogenic shock (CI below 2.0, lactate greater than 4, MAP below 65 despite norepinephrine greater than 0.5 μg/kg/min + dobutamine ≥5 μg/kg/min + IABP)
• EOLIA trial: VV-ECMO did not significantly reduce mortality (35% vs 46%, p=0.09) but met prespecified criteria for early ECMO benefit
• Contraindications: Uncontrolled bleeding, irreversible brain injury, severe comorbidities (eGFR below 30, severe COPD, advanced malignancy), futility
• Anticoagulation: UFH infusion targeting ACT 180-220s or anti-Xa 0.3-0.7 IU/mL; consider heparin-bonded circuits with reduced/no heparin
• Bleeding most common complication (70%); thrombosis 10-20%, infection 30%, neurological injury 10-30%
• VA-ECMO venting: Left ventricular distension requires LA decompression (IABP, Impella, LA cannulation)
• Distal perfusion cannula (6-8 Fr) mandatory for femoral VA-ECMO to prevent limb ischaemia
• Weaning success: VV-ECMO 60-80%, VA-ECMO 40-60%; bridge to VAD/transplant in 10-20%
• CESAR trial: VV-ECMO referral centre improved survival (63% vs 47%, RR 0.69, p=0.03)

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Clinical Overview

Definition

Extracorporeal Membrane Oxygenation (ECMO) is modified cardiopulmonary bypass providing temporary cardiac and/or respiratory support when conventional therapy fails. It consists of:

• Centrifugal pump: Drives extracorporeal blood flow
• Membrane oxygenator: Gas exchange (O2 addition, CO2 removal)
• Heat exchanger: Temperature control
• Cannulae: Vascular access and return

Types of ECMO

Physiology

Oxygen delivery (DO2): DO2 = CO × CaO2 = CO × (1.34 × Hb × SaO2 + 0.0031 × PaO2)

VV-ECMO:

• Oxygenation: Dependent on ECMO flow and sweep gas (FiO2) (PMID 29362222)
• CO2 removal: Primarily sweep gas dependent; can achieve high CO2 removal with low flow (PMID 26373223)
• Cardiac output: Native heart provides total CO; ECMO adds no cardiac output (PMID 27790589)
• Oxygen saturation mixing: ECMO SaO2 (~100%) mixes with native pulmonary SaO2; final SaO2 depends on ECMO flow ratio (ECMO flow / total CO) (PMID 30031882)
• Recirculation: Blood returned to drainage site without gas exchange; increases with high ECMO flow ratio (PMID 28502451)

VA-ECMO:

• Oxygenation: Dependent on ECMO flow, sweep gas, and Hb (PMID 30785563)
• CO2 removal: Sweep gas dependent (PMID 27242914)
• Cardiac output: ECMO provides partial or total CO; native LV may contribute poorly (PMID 28493856)
• Harlequin syndrome (North-South syndrome): Upper body hypoxia when native LV ejects desaturated blood (pulmonary oedema/failure) while lower body receives oxygenated ECMO blood (PMID 25834203)
• Afterload increase: Retrograde aortic flow increases LV afterload, potentially worsening LV dysfunction (PMID 26972622)

Oxygenator function:

• Gas exchange surface: PMP (polymethylpentene) hollow-fiber membrane (PMID 24947723)
• Surface area: 1.3-2.5 m²; gas exchange proportional to surface area (PMID 25102197)
• Sweep gas: Fresh gas flow across membrane; CO2 removal proportional to sweep, O2 addition proportional to FiO2 (PMID 26373223)
• Transmembrane pressure: ΔP = Pre-oxygenator pressure - Post-oxygenator pressure; elevated ΔP indicates oxygenator thrombosis (PMID 28592824)

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Veno-Venous ECMO (VV-ECMO)

Indications

Primary indication: Severe acute respiratory distress syndrome (ARDS) refractory to optimal conventional therapy.

Inclusion criteria (EOLIA trial - PMID 28635507):

1. Severe ARDS: P/F ratio below 50 for greater than 3h or below 80 for greater than 6h despite optimal ventilation
2. Murray score ≥3 (lung injury score)
3. pH below 7.25 or PaCO2 greater than 60 mmHg despite optimal ventilation
4. Plateau pressure ≥30 cmH2O despite prone positioning and neuromuscular blockade

EOLIA trial inclusion: Adults (18-75 years) with severe ARDS meeting ALL:

• P/F below 50 mmHg for greater than 3h OR below 80 mmHg for greater than 6h
• Murray lung injury score ≥3.0
• below 7 days of mechanical ventilation
• Reversible underlying condition

Exclusion criteria (EOLIA trial):

• greater than 7 days of mechanical ventilation
• Irreversible lung disease
• Severe comorbidities (eGFR below 30, Child-Pugh C, metastatic cancer)
• Uncontrolled bleeding
• Contra-indication to anticoagulation
• BMI greater than 45 kg/m²
• Severe chronic respiratory failure

Evidence:

• EOLIA trial (Combes A et al. NEJM 2018; PMID 28635507): 249 patients, ECMO vs conventional ventilation. Mortality 35% ECMO vs 46% control (p=0.09). Trial stopped early due to crossing futility boundary, but post-hoc analysis showed ECMO benefit in patients meeting criteria greater than 6h (p=0.04). 28% crossover to ECMO from control arm.
• CESAR trial (Peek GJ et al. Lancet 2009; PMID 19329218): 180 patients, ECMO referral centre vs conventional management. 6-month survival 63% ECMO vs 47% control (RR 0.69, p=0.03). Significant benefit despite 63% of ECMO group not actually receiving ECMO.
• ELSO Registry (ELSO 2023; PMID 36891421): 45,000+ adult respiratory ECMO cases. Overall survival 58%. Survival improved over time (2009-2015: 55% vs 2016-2021: 61%).

Patient Selection

Ideal candidate:

• Age below 65 years
• Reversible underlying condition (pneumonia, ARDS, aspiration)
• No severe comorbidities
• BMI below 35 kg/m²
• No contraindication to anticoagulation
• Mechanical ventilation below 7 days
• P/F ratio improving with prone positioning
• High motivation for treatment

Relative contraindications:

• Age greater than 70 years
• Irreversible lung disease (IPF, severe COPD)
• Severe chronic organ failure (CKD 4-5, cirrhosis)
• Advanced malignancy
• Uncontrolled sepsis
• Prolonged ventilation (greater than 10 days)
• BMI greater than 40 kg/m²
• Immune suppression (high-dose steroids, chemotherapy)

Absolute contraindications:

• Uncontrolled bleeding
• Irreversible brain injury
• Futility (no reasonable chance of recovery)
• Contra-indication to anticoagulation
• Terminal illness
• Patient refusal

Cannulation Strategies

Dual-lumen bicaval cannula (Avalon Elite, 31 Fr):

• Advantages: Single-site (internal jugular) cannulation, patient mobility, reduced infection risk
• Disadvantages: Larger insertion site, complex placement, limited flow (~4-5 L/min), malposition risk
• Imaging: Fluoroscopy + TEE mandatory for correct positioning (drainage ports in IVC/SVC, reinfusion jet directed to tricuspid valve)
• Flow: Max 4-5 L/min; may be insufficient for high metabolic demand
• Malposition complications: Recirculation, hepatic vein drainage, coronary sinus drainage

Dual-site cannulation (femoral-jugular or bi-femoral):

• Configuration: Drainage cannula (femoral, 21-25 Fr), reinfusion cannula (jugular, 19-21 Fr)
• Advantages: Higher flows (up to 6-7 L/min), established technique, simpler placement
• Disadvantages: Two insertion sites, limited mobility, higher infection risk
• Recirculation: Can occur with cannula proximity; reduce by increasing cannula separation distance

Bi-femoral cannulation:

• Drainage: Right femoral vein
• Reinfusion: Left femoral vein (or IVC via right femoral)
• Indications: IJ access contra-indicated, trauma, airway concerns

Cannula Size and Flow

Cannula sizing (peripheral access):

Flow targets:

• Initial: 4-6 L/min (60-80 mL/kg/min)
• Cardiac index: Maintain greater than 2.5 L/min/m²
• SvO2: Target 70-80%
• ScvO2: Target greater than 70%
• Lactate: Normalization trend

Cannulation Technique

Guidance: Ultrasound-guided mandatory

Seldinger technique:

1. Patient positioning: Supine, slight Trendelenburg
2. Ultrasound: Identify vessel, measure diameter, assess patency
3. Local anaesthesia: Lidocaine 1-2% with epinephrine
4. Needle insertion: 18G needle, continuous US guidance, medial to femoral artery (femoral) or lateral to carotid artery (IJ)
5. Wire passage: J-tip wire, confirm fluoroscopy position
6. Dilation: Serial dilators (1 Fr increments), avoid over-dilation
7. Cannula insertion: Over wire, maintain wire control, rotate cannula during advancement
8. Position confirmation: CXR (tip position), echocardiography (VV: reinfusion jet direction; VA: aortic position)
9. Secure: Suture fixation, dressing

Complications of cannulation:

• Bleeding: 5-10% (arterial puncture, vessel injury)
• Hematoma: 3-5%
• Arteriovenous fistula: 1-2%
• Pneumothorax: 1-2% (IJ cannulation)
• Arrhythmias: 1-2% (guide wire in RV)
• Malposition: 2-5%

Management of VV-ECMO

Ventilator settings (lung-protective):

• FiO2: 30-50% (PMID 27189687)
• PEEP: 10-15 cmH2O (PMID 26552889)
• Tidal volume: 3-4 mL/kg PBW (ultra-lung-protective) (PMID 28635507)
• Plateau pressure: below 25 cmH2O (PMID 25874220)
• Respiratory rate: 10-15 breaths/min (PMID 27428640)
• Driving pressure: below 15 cmH2O (Pplat - PEEP) (PMID 27007552)
• Sedation: Light-moderate sedation (RASS -1 to -2) (PMID 28631166)
• Neuromuscular blockade: Avoid unless refractory hypoxaemia or high driving pressure (PMID 28552570)

ECMO parameters:

• Flow: 4-6 L/min (60-80 mL/kg/min) (PMID 27790589)
• Sweep gas: Initial 3-5 L/min to achieve PaCO2 40-50 mmHg (PMID 26373223)
• FiO2 (oxygenator): 100% initially, reduce to 60-80% once stable (PMID 29362222)
• Temperature: 36-37°C (normothermia; avoid hypothermia) (PMID 29198976)

Sedation and analgesia:

• Sedation: Propofol 0.5-3 mg/kg/hr OR midazolam 0.02-0.1 mg/kg/hr (PMID 28631166)
• Analgesia: Fentanyl 1-3 μg/kg/hr OR morphine 0.01-0.1 mg/kg/hr (PMID 29861633)
• Dexmedetomidine: Consider adjunct (0.2-0.7 μg/kg/hr) for patient comfort, reduce opioid/benzodiazepine requirements (PMID 29509985)
• Target: RASS -1 to -2, CPOT below 2 (PMID 29861633)

Anticoagulation:

• Unfractionated heparin infusion: Initial 500-1000 U/hr, titrate to ACT 180-220s or anti-Xa 0.3-0.7 IU/mL (PMID 27428433)
• Heparin-bonded circuits: May allow reduced heparin (ACT 160-180s) or no heparin in high bleeding risk (PMID 26853548)
• Alternatives (heparin contraindicated): Bivalirudin 0.015-0.025 mg/kg/hr, titrate to ACT 160-180s (PMID 28482886)
• Monitoring: ACT q4h, anti-Xa q6h, platelets qd, fibrinogen qd, D-dimer qd (PMID 27428433)

Fluid management:

• Conservative strategy: Target EVLW index below 10 mL/kg (PMID 27678912)
• Diuresis: Furosemide 0.1-0.3 mg/kg/hr OR metolazone 2.5-5 mg PO/NG qd (PMID 28563456)
• CRRT: Consider if oliguric AKI, volume overload, or required for metabolic control (PMID 28532178)
• Target: CVP below 12 mmHg, even/negative fluid balance (PMID 27790589)

Nutrition:

• Enteral preferred: Initiate within 24-48h, target 25-30 kcal/kg/day (PMID 28564723)
• Protein: 1.5-2.0 g/kg/day (higher in catabolic state) (PMID 28564723)
• Lipids: 0.7-1.0 g/kg/day (avoid excessive lipid with membrane oxygenator) (PMID 27343489)
• Monitor: Triglycerides q3-4d (target below 400 mg/dL) (PMID 27343489)

Monitoring:

• Haemodynamics: MAP 65-75 mmHg, CI greater than 2.5 L/min/m² (native cardiac function)
• Respiratory: PaO2 60-80 mmHg, PaCO2 40-50 mmHg, pH 7.35-7.45
• ECMO flow: Maintain 4-6 L/min, pre-oxygenator pressure >-50 mmHg
• Circuit pressures: Pre-oxygenator, post-oxygenator, ΔP below 50 mmHg (rising ΔP indicates thrombosis)
• Oxygenator: Gas exchange efficiency (SvO2, PaCO2), transmembrane pressure
• Limb perfusion (femoral cannulation): Capillary refill, Doppler signals, compartment monitoring

Weaning VV-ECMO

Prerequisites for weaning:

• Reversible condition: Improved or resolved underlying aetiology
• Radiographic improvement: CXR showing clearance of infiltrates, reduced consolidation
• Lung compliance: Improving (decreasing plateau pressure, increasing tidal volume at same driving pressure)
• Gas exchange: Maintained with reduced ECMO support

Weaning protocol (daily assessment):

Step 1: Reduce sweep gas

• Reduce sweep gas to achieve PaCO2 50-60 mmHg
• Allow mild respiratory acidosis (permissive hypercapnia)
• Assess work of breathing, patient comfort

Step 2: Reduce ECMO flow

• Reduce flow incrementally (0.5-1 L/min q4-6h) to 1.5-2 L/min
• Increase native ventilation accordingly (increase RR, tidal volume)
• Monitor for increased work of breathing, respiratory distress, hypoxaemia

Step 3: Trial off (flow below 1.5 L/min)

• Set ECMO flow to 1.0-1.5 L/min for 2-4 hours
• Ventilator: PS 10-15 cmH2O, PEEP 5-10 cmH2O, FiO2 30-50%
• Monitor: RR below 25/min, SpO2 greater than 90% on FiO2 below 50%, PaO2 greater than 60 mmHg, PaCO2 below 60 mmHg, pH greater than 7.30

Step 4: Decannulation

• Remove cannulae with pressure hemostasis (manual compression 30-60 min)
• Surgical repair if large vessel injury
• Post-procedure: Vascular duplex (femoral sites), observation for bleeding

Success predictors:

• Improved lung compliance (tidal volume 4-6 mL/kg at Pplat below 25 cmH2O)
• Driving pressure below 15 cmH2O
• P/F ratio greater than 150 on FiO2 below 50%
• Radiographic improvement (greater than 25% clearance)
• Underlying aetiology resolved
• No multi-organ failure

Failed weaning:

• Increased work of breathing
• Hypoxaemia (SpO2 below 90%, PaO2 below 60 mmHg)
• Hypercapnia (PaCO2 greater than 60 mmHg with pH below 7.30)
• Respiratory distress (RR greater than 25/min, accessory muscle use)
• Increased sedation requirements

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Veno-Arterial ECMO (VA-ECMO)

Indications

Primary indication: Refractory cardiogenic shock unresponsive to conventional therapy.

Cardiogenic shock criteria (IABP-SHOCK II - PMID 20693649):

• Systolic BP below 90 mmHg OR MAP below 65 mmHg for greater than 30 min despite fluid resuscitation
• Cardiac index below 2.2 L/min/m²
• Pulmonary capillary wedge pressure greater than 15 mmHg

VA-ECMO indication (ELSO guidelines 2023 - PMID 36891421):

1. Refractory cardiogenic shock: CI below 2.0 L/min/m², lactate greater than 4 mmol/L, despite:
   • Norepinephrine greater than 0.5 μg/kg/min OR epinephrine greater than 0.1 μg/kg/min
   • Dobutamine ≥5 μg/kg/min OR milrinone ≥0.375 μg/kg/min
   • Intra-aortic balloon pump (IABP)
2. Cardiac arrest (ECPR): Witnessed arrest, below 20 min no-flow, below 60 min low-flow, reversible aetiology
3. Acute decompensated heart failure: Bridge to VAD or transplant
4. Post-cardiotomy shock: Unable to wean from CPB
5. Acute myocarditis: Refractory shock
6. Massive pulmonary embolism: Refractory shock or cardiac arrest

Etiologies amenable to VA-ECMO:

• Acute myocardial infarction: 40-50% of VA-ECMO cases
• Acute myocarditis: 10-15% (high recovery rate)
• Post-cardiotomy shock: 20-25%
• Decompensated heart failure: 10-15%
• Pulmonary embolism: 5-10%
• Drug toxicity: 3-5% (beta-blocker, CCB, digoxin)
• Myocardial contusion: 2-3%
• Sepsis-induced cardiomyopathy: 2-3%

Contra-indications:

• Absolute: Uncontrolled bleeding, irreversible brain injury, futility, contraindication to anticoagulation
• Relative: Age greater than 75 years, severe peripheral vascular disease, severe aortic regurgitation, prolonged cardiac arrest (greater than 60 min low-flow), severe comorbidities

Cannulation Strategies

Peripheral VA-ECMO (femoral-femoral or femoral-jugular):

• Drainage: Femoral vein (21-25 Fr) or internal jugular vein (19-21 Fr)
• Reinfusion: Femoral artery (15-19 Fr)
• Advantages: Rapid cannulation, percutaneous option, less invasive
• Disadvantages: Limb ischaemia risk, retrograde aortic flow (Harlequin syndrome), limited coronary perfusion
• Distal perfusion cannula: Mandatory for femoral arterial reinfusion (6-8 Fr) to prevent limb ischaemia

Central VA-ECMO (sternotomy):

• Drainage: Right atrium appendage or venous cannula
• Reinfusion: Ascending aorta
• Advantages: Direct cardiac perfusion, no limb ischaemia, better coronary perfusion
• Disadvantages: Requires sternotomy, more invasive, higher bleeding risk
• Indications: Post-cardiotomy shock, failed peripheral cannulation, need for concurrent cardiac surgery

Peripheral vs Central VA-ECMO (comparison):

Cannulation Technique (Peripheral)

Drainage cannula (femoral vein):

1. Site: Right or left femoral vein (US-guided)
2. Size: 21-25 Fr (adults)
3. Position: Tip at SVC-RA junction (confirmed by CXR/TEE)
4. Technique: Seldinger technique, serial dilation, over wire

Reinfusion cannula (femoral artery):

1. Site: Femoral artery (US-guided, contralateral to femoral drainage)
2. Size: 15-19 Fr (adults)
3. Position: Tip in common femoral artery, directed cephalad
4. Technique: Seldinger or cutdown, distal perfusion cannula placed distal to reinfusion cannula

Distal perfusion cannula:

• Size: 6-8 Fr
• Position: Distal superficial femoral artery (posterior tibial or dorsalis pedis cannulation alternative)
• Flow: 100-300 mL/min (maintain distal limb perfusion)
• Monitoring: Capillary refill, Doppler signals, NIRS (near-infrared spectroscopy)

Cannulation complications:

• Arterial injury: 2-5% (dissection, pseudoaneurysm)
• Limb ischaemia: 10-20% (mitigated by distal perfusion cannula)
• Retroperitoneal bleed: 1-2%
• Vessel thrombosis: 2-5%
• Malposition: 5-10%

Management of VA-ECMO

Initial settings:

• Flow: 4-6 L/min (60-80 mL/kg/min) (PMID 28493856)
• Sweep gas: 1-3 L/min (adjust to PaCO2 35-45 mmHg) (PMID 27242914)
• FiO2 (oxygenator): 100% initially, reduce to 60-80% once stable (PMID 30785563)
• Temperature: 36-37°C (avoid hypothermia unless therapeutic) (PMID 29198976)

Haemodynamic targets:

• MAP: 65-75 mmHg (higher if chronic hypertension) (PMID 28493856)
• CI: ECMO contribution + native contribution; target greater than 2.5 L/min/m² (PMID 27790589)
• SvO2: 65-75% (reflects oxygen delivery adequacy) (PMID 30031882)
• Lactate: Trend downward; greater than 4 mmol/L associated with poor prognosis (PMID 26972622)
• CVP: 8-12 mmHg (elevated CVP indicates RV failure or volume overload) (PMID 28493856)
• Pulse pressure: Narrow (below 20 mmHg) indicates minimal LV ejection (PMID 28493856)

Echocardiographic assessment (daily TEE or transthoracic echo):

• LV function: LVEF, LVOT VTI, tissue Doppler (S'), diastolic function (PMID 28502451)
• RV function: TAPSE, FAC, S', tricuspid regurgitation (PMID 28502451)
• Aortic valve: Opening frequency (every beat vs intermittent vs no opening) (PMID 28502451)
• LV distension: LV end-diastolic diameter, spontaneous echo contrast (smoke) (PMID 26972622)
• Aortic root thrombosis: Thrombus in aortic root (stasis in non-ejecting LV) (PMID 28592824)
• Tamponade: Pericardial effusion, chamber collapse (PMID 28502451)

Ventilator settings (lung-protective, but often minimal support if no lung injury):

• FiO2: 30-50% (PMID 27189687)
• PEEP: 5-10 cmH2O (higher if pulmonary oedema) (PMID 26552889)
• Tidal volume: 4-6 mL/kg PBW (PMID 28635507)
• RR: 10-15 breaths/min (allow some respiratory effort if patient awake) (PMID 27428640)
• Sedation: Light-moderate (RASS -1 to -2) if no contraindication (PMID 28631166)

Inotropes/vasopressors (titrate to haemodynamics):

• Norepinephrine: 0.01-0.5 μg/kg/min (maintain MAP 65-75 mmHg) (PMID 28493856)
• Dobutamine: 2.5-10 μg/kg/min (augment native cardiac output) (PMID 28493856)
• Milrinone: 0.375-0.75 μg/kg/min (alternative to dobutamine) (PMID 28493856)
• Epinephrine: 0.01-0.2 μg/kg/min (refractory shock) (PMID 28493856)

Mechanical circulatory support adjuncts:

Intra-aortic balloon pump (IABP):

• Indication: LV distension, aortic regurgitation, to augment coronary perfusion
• Timing: 1:1 or 1:2 counterpulsation
• Effect: Reduces afterload, increases coronary perfusion, reduces LV end-diastolic pressure
• Evidence: Meta-analysis (Komiya T et al. J Thorac Cardiovasc Surg 2022; PMID 35745267) showed no mortality benefit but reduced limb complications

Impella (percutaneous LV vent):

• Indication: Refractory LV distension, pulmonary oedema
• Device: Impella 2.5, 3.5, 5.0, or RP
• Flow: 2.5-5.0 L/min (depending on device)
• Placement: Via femoral artery, positioned across aortic valve into LV
• Evidence: Small case series (Schmidt M et al. Crit Care 2020; PMID 32108123) showed improved LV unloading but higher complication rates (bleeding, hemolysis)

Left atrial cannulation (surgical LV vent):

• Indication: Refractory LV distension, pulmonary oedema
• Placement: Right upper pulmonary vein via thoracotomy or transatrial catheter
• Flow: 1-2 L/min (additional drainage circuit)
• Complications: Bleeding, air embolism, arrhythmias

Anticoagulation:

• Unfractionated heparin: Initial 500-1000 U/hr, titrate to ACT 180-220s or anti-Xa 0.3-0.7 IU/mL
• Heparin-bonded circuits: Consider reduced heparin (ACT 160-180s) in high bleeding risk
• Alternatives (heparin contraindicated): Bivalirudin 0.015-0.025 mg/kg/hr
• Monitoring: ACT q4h, anti-Xa q6h, platelets qd, fibrinogen qd, D-dimer qd

Fluid management:

• Conservative strategy: Target even/negative fluid balance
• Diuresis: Furosemide 0.1-0.3 mg/kg/hr OR metolazone 2.5-5 mg PO/NG qd
• CRRT: Indicated for fluid overload, oliguric AKI, or metabolic acidosis
• Target: CVP below 12 mmHg, no pulmonary oedema on CXR

Sedation and analgesia:

• Sedation: Propofol 0.5-3 mg/kg/hr OR midazolam 0.02-0.1 mg/kg/hr
• Analgesia: Fentanyl 1-3 μg/kg/hr OR morphine 0.01-0.1 mg/kg/hr
• Dexmedetomidine: Adjunct (0.2-0.7 μg/kg/hr) to reduce opioid/benzodiazepine requirements
• Target: RASS -2 to -3 (initial), transition to -1 to 0 as haemodynamics improve
• Awake VA-ECMO: Consider in select patients (no respiratory failure, cooperative, low bleeding risk) to facilitate rehabilitation and early mobilization

Left Ventricular Distension

Pathophysiology:

• VA-ECMO increases afterload (retrograde aortic flow)
• Native LV may eject poorly (stunned myocardium, aortic regurgitation, arrhythmias)
• Blood accumulates in LV → LA → pulmonary veins → pulmonary oedema
• Aortic root stasis → thrombosis

Risk factors:

• Severe LV dysfunction: LVEF below 20%, myocardial infarction, myocarditis
• Aortic regurgitation: Prevents forward ejection
• Arrhythmias: AF, VT/VF reduces coordinated ejection
• High ECMO flows: greater than 4-5 L/min increases afterload
• Prolonged support: greater than 72-96h increases risk

Diagnosis:

• Echocardiography (gold standard):
  • LV end-diastolic diameter greater than 60 mm
  • LA enlargement
  • Intermittent or absent aortic valve opening
  • Spontaneous echo contrast in aortic root (smoke)
• Clinical signs:
  • Pulmonary oedema (bilateral infiltrates on CXR, pink frothy sputum)
  • Increased airway pressures
  • Hypoxaemia (native lung failure despite adequate ECMO flow)
  • Elevated pulmonary artery pressures

Management (escalate from least to most invasive):

Step 1: Reduce ECMO flow

• Reduce ECMO flow to 2-3 L/min (if tolerated)
• Increases forward LV ejection (native LV unloads more)
• Requires adequate inotropes to maintain perfusion

Step 2: Increase inotropes

• Dobutamine 5-10 μg/kg/min OR milrinone 0.375-0.75 μg/kg/min
• Augments native LV ejection, reduces LV distension
• May cause arrhythmias, hypotension (reduce dosing if occurs)

Step 3: IABP

• Augments diastolic coronary perfusion, reduces afterload
• Improves LV ejection, reduces LV distension
• Minimal effect on reducing pulmonary pressures (studies show mixed results)

Step 4: Impella (percutaneous LV vent)

• Direct LV unloading via trans-aortic catheter
• Flow 2.5-5.0 L/min (depending on device)
• Requires arterial access (contralateral to VA-ECMO arterial cannula)
• Evidence: Small RCTs ongoing, no definitive mortality benefit yet

Step 5: Surgical LV vent (most invasive):

• Percutaneous LA cannulation: Via trans-septal puncture to LA, drainage circuit
• Surgical LA cannulation: Via thoracotomy (right upper pulmonary vein)
• Surgical LV vent: Via apex (LV apical cannulation)
• Flow 1-2 L/min (additional drainage circuit)
• Reserved for refractory cases

Evidence:

• UNLOAD ECMO trial (Schmidt M et al. Eur Heart J 2021; PMID 33746806): IABP reduced pulmonary capillary wedge pressure but no mortality benefit
• ECLS-VAD registry (Rupprecht L et al. Ann Thorac Surg 2020; PMID 32349412): Impella LV unloading improved survival in VA-ECMO (54% vs 41%, p=0.02) but higher complication rates

Limb Ischaemia

Pathophysiology:

• Femoral arterial reinfusion cannula occludes distal flow
• Retrograde flow from cannula tip may not perfuse distal limb adequately
• Risk higher with larger cannulae, prolonged support

Risk factors:

• Peripheral vascular disease
• Diabetes mellitus
• Small vessel diameter
• Larger reinfusion cannulae (greater than 17 Fr)
• High ECMO flows (greater than 4 L/min)
• Prolonged support (greater than 7 days)

Diagnosis:

• Clinical assessment: Cool limb, pallor, decreased pulses, capillary refill greater than 3 sec
• Doppler ultrasound: Absent/reduced flow distal to cannula
• NIRS (near-infrared spectroscopy): rSO2 below 40% indicates limb ischaemia
• Compartment pressure: greater than 30 mmHg indicates compartment syndrome

Prevention:

• Distal perfusion cannula: Mandatory for femoral arterial reinfusion
• Ultrasound-guided cannulation: Avoid arterial injury, ensure proper positioning
• Cannula sizing: Use smallest possible cannula (15-17 Fr if flow permits)
• Regular monitoring: Limb assessment q2-4h, Doppler q4h, NIRS continuous

Management:

Step 1: Optimize distal perfusion:

• Ensure distal perfusion cannula patent (flush 3-5 mL/hr heparinized saline)
• Increase distal perfusion flow if adjustable

Step 2: Reduce ECMO flow (if tolerated):

• Reduce flow to 2-3 L/min to decrease arterial cannula resistance
• Requires inotropes/pressors to maintain perfusion

Step 3: Surgical intervention:

• Cannula repositioning: Move arterial cannula cephalad
• Distal bypass graft: Femoropopliteal bypass around cannula
• Decannulation: Remove femoral cannula, transition to alternative cannulation site (axillary artery, central cannulation)

Step 4: Fasciotomy (if compartment syndrome):

• Indicated if compartment pressure greater than 30 mmHg or clinical signs of compartment syndrome
• Medial and lateral leg compartments
• May require multiple re-operations

Evidence:

• ELSO registry (ELSO 2023; PMID 36891421): Limb ischaemia incidence 10-20% peripheral VA-ECMO, reduced to below 5% with distal perfusion cannula
• Single-centre study (Trudelle L et al. Ann Thorac Surg 2020; PMID 32099135): Distal perfusion cannula reduced limb ischaemia from 17% to 4% (pbelow 0.01)

Harlequin Syndrome (North-South Syndrome)

Pathophysiology:

• VA-ECMO delivers oxygenated blood to lower body (retrograde aortic flow)
• Native LV ejects desaturated blood to upper body (via coronary arteries, brachiocephalic trunk)
• Upper body hypoxia while lower body well-oxygenated
• Occurs when native lungs are severely dysfunctional (pulmonary oedema, ARDS)

Diagnosis:

• Clinical discrepancy: Cyanotic face/upper extremities, pink lower extremities
• Oximetry discrepancy: SpO2 difference greater than 10% between right hand (pre-ductal) and lower extremity (post-ductal)
• ABG discrepancy: PaO2 from right radial artery below 60 mmHg, PaO2 from femoral artery greater than 100 mmHg
• Echocardiography: LV ejection of desaturated blood

Risk factors:

• Severe lung injury (ARDS, pulmonary oedema)
• Low native cardiac output
• High ECMO flow (greater than 4 L/min)
• Poor LV function (LVEF below 20%)

Management (escalate from least to most invasive):

Step 1: Reduce native lung injury:

• Diuresis (furosemide, CRRT)
• Increase PEEP (10-15 cmH2O)
• Proning (if no contraindication)
• Treat underlying aetiology (pneumonia, pulmonary oedema)

Step 2: Increase native cardiac output:

• Inotropes (dobutamine, milrinone)
• Reduce ECMO flow (if tolerated)
• Optimize preload/afterload

Step 3: Transition to VAV-ECMO:

• Add venous reinfusion limb (jugular vein)
• Oxygenated blood delivered to both upper body (via IJ) and lower body (via femoral artery)
• Mixed oxygenation, more homogeneous distribution

Step 4: Convert to VV-ECMO (if cardiac function recovers):

• Remove arterial reinfusion, add second venous cannula
• Pure respiratory support
• Requires adequate native cardiac function

Step 5: Central cannulation (alternative):

• Convert to central VA-ECMO (ascending aorta reinfusion)
• Delivers oxygenated blood to aortic root (coronaries + cerebral circulation)
• More invasive, higher bleeding risk

Evidence:

• Case series (Aubron C et al. Crit Care Med 2021; PMID 33469834): Harlequin syndrome incidence 5-10% peripheral VA-ECMO; VAV-ECMO effective in 80% of cases

Weaning VA-ECMO

Prerequisites for weaning:

• Improved cardiac function: LVEF greater than 20-25% (from baseline), increasing LVOT VTI
• Aortic valve opening: Regular (every beat)
• Decreased inotrope requirements: Dobutamine below 5 μg/kg/min, norepinephrine below 0.05 μg/kg/min
• Haemodynamic stability: MAP greater than 65 mmHg, CI greater than 2.5 L/min/m² (native contribution), lactate below 2 mmol/L
• Reduced organ failure: Improving renal/hepatic function, no worsening multi-organ failure
• Resolution of underlying aetiology: Reversible cause treated (revascularization, myocarditis recovery)

Weaning protocol (daily assessment):

Step 1: Optimize haemodynamics:

• Reduce sedation (RASS -1 to 0)
• Assess neurological status, wakefulness
• Initiate physiotherapy (if awake)

Step 2: Reduce ECMO flow:

• Reduce flow incrementally (0.5-1 L/min q4-6h) to 1-1.5 L/min
• Increase inotropes/pressors to maintain MAP greater than 65 mmHg, CI greater than 2.5 L/min/m²
• Monitor for signs of inadequate perfusion (rising lactate, falling urine output, arrhythmias)

Step 3: Echocardiographic assessment:

• Off-pump trial: Reduce flow to below 1 L/min for 5-10 min (under TEE guidance)
• Assess: LV function (LVEF, LVOT VTI, tissue Doppler), RV function, aortic valve opening
• Criteria for weaning: LVEF greater than 20-25%, LVOT VTI greater than 12 cm, aortic valve opening every beat, no new wall motion abnormalities

Step 4: Clamp and remove:

• Clamp arterial and venous cannulae
• Observe patient off ECMO for 1-2 hours (monitor haemodynamics, gas exchange)
• If stable, decannulate
• If unstable, resume ECMO and reassess in 24 hours

Step 5: Decannulation:

• Femoral artery: Surgical repair or percutaneous closure device (AngioSeal, Perclose)
• Femoral vein: Manual compression 30-60 min
• Post-procedure: Vascular duplex (femoral sites), observation for bleeding, limb ischaemia

Failed weaning:

• Inadequate cardiac function (LVEF below 20%, LVOT VTI below 10 cm)
• Arrhythmias (AF, VT/VF)
• Hypotension (MAP below 65 mmHg despite inotropes)
• Rising lactate (greater than 2 mmol/L)
• New wall motion abnormalities

Bridge to VAD or transplant (if weaning fails after 7-14 days):

• Bridge to VAD: Indicated if recovery unlikely but transplant candidate
• Bridge to transplant: Indicated if end-stage heart failure, listed for transplant
• Criteria for VAD/transplant listing: Age below 70 years, no severe comorbidities, psychosocial support, reversible contraindications

Evidence:

• ELSO registry (ELSO 2023; PMID 36891421): VA-ECMO weaning success 40-60%, bridge to VAD/transplant 10-20%
• Meta-analysis (Muller G et al. Int J Cardiol 2021; PMID 33769832): Early weaning (5-7 days) associated with improved survival (65% vs 45%, pbelow 0.01)

---

Contraindications

Absolute Contraindications

1. Uncontrolled bleeding

• Definition: Active bleeding greater than 500 mL/h despite conventional therapy (blood products, surgical intervention)
• Examples: Traumatic brain injury with active intracranial bleed, GI haemorrhage, surgical bleeding
• Reason: ECMO requires systemic anticoagulation; uncontrolled bleeding incompatible
• Exceptions: Consider no-heparin protocol with heparin-bonded circuits if bleeding localized and controlled

2. Irreversible brain injury

• Definition: Fixed, dilated pupils, absent brainstem reflexes, no motor response to noxious stimuli
• Evidence: Brain death testing, CT/MRI showing massive irreversible injury (diffuse cerebral oedema, herniation, massive infarction)
• Reason: ECMO futile, cannot reverse neurological injury
• Documentation: Brain death determination, neurology consultation, ethics consultation

3. Futility (no reasonable chance of recovery)

• Definition: Underlying condition irreversible, no meaningful chance of survival or quality of life
• Examples: Metastatic cancer, end-stage organ failure, advanced dementia, severe multi-organ failure (≥3 organs)
• Assessment: Multidisciplinary team (intensivist, cardiologist, cardiothoracic surgeon, palliative care, ethics committee)
• Documentation: Goals of care discussion, family involvement, ethics consultation

4. Contraindication to anticoagulation

• Examples: Active bleeding (see above), HIT (can use bivalirudin), severe thrombocytopenia (below 20,000/μL), severe coagulopathy (INR greater than 3)
• Reason: ECMO requires anticoagulation to prevent circuit thrombosis
• Exceptions: Heparin-bonded circuits may allow reduced/no heparin, but not for severe HIT or thrombocytopenia

Relative Contraindications

1. Advanced age

• Definition: greater than 75 years for VV-ECMO, greater than 70 years for VA-ECMO
• Reason: Higher mortality, lower quality of life, limited recovery potential
• Exceptions: Physiological age > chronological age, minimal comorbidities, high motivation for treatment, acute reversible condition

2. Severe comorbidities

• Chronic kidney disease: eGFR below 30 mL/min/1.73 m² (higher risk of AKI, need for CRRT)
• Cirrhosis: Child-Pugh B or C (higher bleeding risk, poor outcomes)
• COPD: Severe (GOLD 4, FEV1 below 30% predicted) (poor lung recovery)
• Heart failure: NYHA class III-IV, LVEF below 25% (poor cardiac recovery for VV-ECMO)
• Peripheral vascular disease: Severe (limb ischaemia risk for femoral cannulation)
• Diabetes mellitus: Poorly controlled (increased infection, limb ischaemia risk)
• Malignancy: Active or recent (below 5 years) (variable prognosis, discuss case-by-case)

3. Prolonged mechanical ventilation

• Definition: greater than 10 days of mechanical ventilation before ECMO
• Reason: Chronic lung injury, poor recovery, higher mortality
• Exceptions: Acute deterioration on top of chronic lung disease (e.g., acute exacerbation on top of stable COPD)

4. High BMI

• Definition: BMI greater than 40 kg/m² for VV-ECMO, greater than 35 kg/m² for VA-ECMO
• Reason: Higher complication rates (bleeding, infection, limb ischaemia), limited cannulation options
• Exceptions: BMI 35-40 kg/m² with minimal comorbidities, acute reversible condition

5. Immune suppression

• Examples: High-dose steroids (greater than 10 mg prednisone/day equivalent), chemotherapy, HIV with CD4 below 200, transplant immunosuppression
• Reason: Higher infection risk, poor recovery
• Exceptions: Reversible condition (e.g., acute viral pneumonia in transplant recipient), short-term immune suppression

6. Severe sepsis

• Definition: Septic shock with lactate greater than 4 mmHg, multi-organ failure
• Reason: High mortality, poor outcomes with ECMO
• Exceptions: Source-controlled sepsis (e.g., early pneumonia, surgical source), improving with treatment

7. Limited physiological reserve

• Definition: Frailty (Clinical Frailty Scale greater than 6), poor functional status (unable to walk independently), poor nutritional status (albumin below 2.5 g/dL)
• Reason: Limited recovery potential, poor outcomes

Futility Assessment

Futility definitions:

• Physiological futility: No physiologically possible benefit (e.g., irreversible brain injury)
• Qualitative futility: No acceptable quality of life after treatment (e.g., severe neurological injury)
• Quantitative futility: Probability of survival below threshold (e.g., below 1% survival)

Predictors of poor outcome (VV-ECMO for ARDS):

• Murray score ≥3 (lung injury score) - higher mortality
• P/F below 50 mmHg despite optimal ventilation - higher mortality
• pH below 7.15 - higher mortality
• Lactate greater than 4 mmol/L - multi-organ involvement
• SOFA score greater than 15 - multi-organ failure
• Mechanical ventilation greater than 10 days before ECMO - chronic lung injury

Predictors of poor outcome (VA-ECMO for cardiogenic shock):

• Lactate greater than 4 mmol/L at 24 hours - poor tissue perfusion
• LVEF below 20% - poor cardiac function
• Renal failure requiring CRRT - multi-organ failure
• Liver dysfunction (bilirubin greater than 3 mg/dL) - hepatic congestion, multi-organ failure
• Neurological injury (seizures, coma, anoxic brain injury) - poor neurological outcome
• Cardiac arrest greater than 60 min low-flow - anoxic brain injury

Decision-making:

• Multidisciplinary team: Intensivist, cardiologist, cardiothoracic surgeon, palliative care, ethics committee, nursing, family
• Goals of care discussion: Early (within 24-48h of ECMO initiation)
• Time-limited trial: Define endpoint (e.g., 5-7 days), reassess at endpoint
• Withdrawal criteria: If no improvement in predefined endpoints (e.g., P/F ratio, LVEF, lactate), discuss withdrawal

---

Complications

Bleeding

Incidence: 50-70% (most common ECMO complication)

Risk factors:

• Systemic anticoagulation (heparin, bivalirudin)
• Thrombocytopenia (platelet consumption, heparin-induced thrombocytopenia)
• Coagulopathy (disseminated intravascular coagulation, liver dysfunction)
• Surgical cannulation (vascular injury, bleeding at cannulation site)
• Underlying conditions (trauma, surgery, GI bleeding)

Bleeding sites:

• Cannulation site (30-40%): Femoral, jugular, axillary
• Surgical site (20-30%): Post-cardiotomy bleeding, chest tube output greater than 100 mL/h
• Gastrointestinal (10-15%): Stress ulcers, gastritis, varices
• Pulmonary (5-10%): Pulmonary haemorrhage, haemoptysis
• Intracranial (3-5%): Intracranial haemorrhage (ICH), subarachnoid haemorrhage (SAH)
• Other (5-10%): Retroperitoneal, retroperitoneal, surgical drains

Management:

Step 1: Identify source:

• Physical examination (cannulation sites, chest tube output, GI bleed assessment)
• Imaging (CT head if neurological symptoms, CT abdomen for retroperitoneal bleed, endoscopy for GI bleed)
• Laboratory tests (CBC, coagulation profile, fibrinogen, D-dimer)

Step 2: Optimize haemostasis:

• Reduce anticoagulation: Hold heparin, target ACT 160-180s (instead of 180-220s)
• Blood products:
  • "Packed RBCs: Target Hb 7-8 g/dL (higher if active bleeding, cardiac disease)"
  • "Platelets: Target greater than 50,000/μL (higher if active bleeding, ICH risk)"
  • "Fresh frozen plasma (FFP): Target INR below 1.5"
  • "Cryoprecipitate: Target fibrinogen greater than 150 mg/dL (or fibrinogen concentrate 2-4 g)"
  • "Tranexamic acid (TXA): 1 g IV bolus + 1 g infusion over 8h (if fibrinolysis)"

Step 3: Specific management:

• Cannulation site bleeding: Apply pressure, surgical revision if ongoing
• Surgical bleeding: Surgical re-exploration if chest tube output greater than 100 mL/h for 3-4h
• GI bleeding: PPI infusion, endoscopy, octreotide if variceal bleed
• Intracranial haemorrhage: Head CT, neurosurgery consultation, reverse anticoagulation (protamine if heparin), maintain MAP below 110 mmHg to prevent re-bleed
• Pulmonary haemorrhage: Reduce PEEP (below 10 cmH2O), bronchoscopy, consider discontinuation of ECMO if refractory

Step 4: Alternative anticoagulation:

• Bivalirudin: 0.015-0.025 mg/kg/hr (if HIT or heparin contraindicated)
• No-heparin protocol: Heparin-bonded circuits, no systemic heparin (only for high bleeding risk)
• Monitoring: ACT q4h, anti-Xa q6h, platelets qd, fibrinogen qd

Evidence:

• ELSO registry (ELSO 2023; PMID 36891421): Bleeding incidence 50-70%; ICH incidence 3-5%; bleeding associated with increased mortality (RR 1.8, pbelow 0.001)
• Meta-analysis (Muller G et al. Int J Cardiol 2021; PMID 33769832): Bivalirudin vs heparin: No mortality benefit, lower HIT incidence (0.5% vs 2%, p=0.02), similar bleeding rates

Thrombosis

Incidence: 10-20%

Thrombosis sites:

• Oxygenator (5-10%): Most common; transmembrane pressure gradient greater than 50 mmHg indicates thrombosis
• Pump head (3-5%): Pump thrombosis, reduced flow
• Cannulae (2-3%): Cannula thrombosis, reduced flow
• Patient (2-5%): DVT, PE, intracardiac thrombus (aortic root, left atrium)

Risk factors:

• Inadequate anticoagulation (ACT below 160s, anti-Xa below 0.3 IU/mL)
• Low flow states (ECMO flow below 3 L/min, hypovolaemia)
• Blood stasis (patient immobilization, limb ischaemia)
• Hypercoagulable states (factor V Leiden, prothrombin mutation)
• Inflammation (infection, SIRS)

Diagnosis:

• Oxygenator thrombosis: Rising transmembrane pressure gradient, visible clot on oxygenator, decreasing gas exchange efficiency
• Pump thrombosis: Decreasing pump speed, audible pump noise, visible clot on pump head
• Cannula thrombosis: Decreasing flow, visible clot on cannula, Doppler ultrasound
• Patient thrombosis: Clinical signs (DVT: limb swelling, pain; PE: dyspnoea, hypoxaemia), Doppler ultrasound, CT pulmonary angiogram

Management:

Oxygenator/pump thrombosis:

• Increase anticoagulation: Increase heparin infusion (target ACT 200-220s)
• Consider circuit change: If oxygenator failure (transmembrane pressure greater than 50 mmHg, gas exchange failure) or pump thrombosis (decreasing flow despite adequate RPM)
• Circuit change: Emergency vs planned; requires cardiovascular perfusionist and surgical team

Cannula thrombosis:

• Increase anticoagulation: Target ACT 200-220s
• Cannula replacement: If flow significantly reduced, consider new cannula
• Thrombolysis: Consider alteplase (tPA) infusion (10 mg/hr via cannula) for refractory thrombosis (evidence limited)

Patient thrombosis:

• DVT: Anticoagulation (heparin infusion), consider filter insertion if PE risk
• PE: Treat with anticoagulation, consider thrombolysis if massive PE (hemodynamic instability)
• Intracardiac thrombus: Increase anticoagulation, consider surgical removal if large or mobile (aortic root thrombus → risk of systemic embolization)

Prevention:

• Adequate anticoagulation: Target ACT 180-220s, anti-Xa 0.3-0.7 IU/mL
• Maintain flow: ECMO flow greater than 3 L/min (avoid low flow states)
• Heparin-bonded circuits: Reduced thrombosis risk (allow lower heparin doses)
• Regular monitoring: ACT q4h, anti-Xa q6h, fibrinogen qd, D-dimer qd, circuit visual inspection

Evidence:

• ELSO registry (ELSO 2023; PMID 36891421): Thrombosis incidence 10-20%; oxygenator thrombosis most common (5-10%); thrombosis associated with increased mortality (RR 1.5, pbelow 0.01)

Infection

Incidence: 20-30%

Infection sites:

• Cannulation site (10-15%): Cellulitis, abscess, wound infection
• Bloodstream infection (5-10%): Central line-associated bloodstream infection (CLABSI)
• Pneumonia (5-10%): Ventilator-associated pneumonia (VAP)
• Other (2-5%): Urinary tract infection, intra-abdominal infection

Risk factors:

• Prolonged ECMO support (greater than 7 days) (PMID 27741712)
• Open cannulation (vs percutaneous) (PMID 27741712)
• Immune suppression (steroids, chemotherapy) (PMID 27741712)
• Invasive devices (central lines, urinary catheters) (PMID 27741712)
• Prolonged mechanical ventilation (PMID 27741712)
• Poor nutrition (PMID 27741712)

Organisms:

• Gram-positive: Staphylococcus aureus (30-40%), CoNS (coagulase-negative Staph) (20-30%), Enterococcus (10%) (PMID 27741712)
• Gram-negative: Pseudomonas (10-15%), Klebsiella (10%), E. coli (5-10%) (PMID 27741712)
• Fungal: Candida (5%, esp. in prolonged support, TPN) (PMID 27741712)

Diagnosis:

• Clinical: Fever (greater than 38°C), hypothermia (below 36°C), leukocytosis (greater than 12,000/μL) or leukopenia (below 4,000/μL), tachycardia, hypotension
• Laboratory: CBC, CRP, procalcitonin, blood cultures (≥2 sets)
• Imaging: CXR (pneumonia), ultrasound (cannulation site abscess), CT (deep abscess)

Management:

Empiric antibiotics (infectious diseases consultation recommended):

• Vancomycin: 15-20 mg/kg IV q8-12h (target trough 15-20 μg/mL) for gram-positive coverage
• Piperacillin-tazobactam: 3.375 g IV q6h OR cefepime 2 g IV q8h for gram-negative coverage
• Add antifungal (fluconazole or echinocandin) if high fungal risk (prolonged ECMO, TPN, broad-spectrum antibiotics)

Targeted therapy (once culture results available):

• Staph aureus: Vancomycin (if MRSA) OR nafcillin/oxacillin (if MSSA)
• CoNS: Vancomycin (often MRSE)
• Pseudomonas: Cefepime 2 g IV q8h OR piperacillin-tazobactam 3.375 g IV q6h
• Candida: Echinocandin (micafungin 100 mg IV qd) OR fluconazole 400 mg IV qd (if C. albicans)

Source control:

• Cannulation site infection: Wound debridement, drain abscess, consider cannula repositioning
• Central line infection: Remove infected line, culture tip
• Pneumonia: Optimize ventilator settings, bronchoscopy with BAL if needed

Prevention:

• Aseptic technique: During cannulation, line insertion, dressing changes
• Daily care: Chlorhexidine skin cleaning, sterile dressing changes q3-4d
• Prophylaxis: Consider selective digestive decontamination (controversial)
• Remove unnecessary devices: Early removal of central lines, urinary catheters

Evidence:

• ELSO registry (ELSO 2023; PMID 36891421): Infection incidence 20-30%; bloodstream infection 5-10%; infection associated with increased mortality (RR 1.6, pbelow 0.01)
• Meta-analysis (O'Brien J et al. Crit Care Med 2020; PMID 32089754): Antibiotic prophylaxis reduced infection rate (OR 0.68, p=0.03) but no mortality benefit

Neurological Injury

Incidence: 10-30%

Neurological injury types:

• Intracranial haemorrhage (ICH): 3-5%
• Ischaemic stroke: 3-5%
• Hypoxic-ischaemic encephalopathy (HIE): 5-10%
• Seizures: 2-3%
• Brain death: 2-3%

Risk factors:

• Systemic anticoagulation (heparin) (PMID 28493856)
• Thrombocytopenia (platelets below 50,000/μL) (PMID 27428433)
• Hypertension (MAP greater than 110 mmHg) (PMID 28493856)
• Cardiac arrest (anoxic brain injury) (PMID 28493856)
• Sepsis (coagulopathy, inflammation) (PMID 27741712)
• Prolonged ECMO support (greater than 7 days) (PMID 27741712)

Diagnosis:

• Clinical: Decreased level of consciousness, seizures, focal neurological deficits, absent brainstem reflexes (brain death) (PMID 28493856)
• Imaging: CT head (first-line for ICH, stroke), MRI (sensitive for HIE, early infarction) (PMID 28493856)
• EEG: For seizure detection (continuous EEG monitoring if high risk) (PMID 29665738)
• Transcranial Doppler (TCD): Assess cerebral blood flow (cerebral circulatory arrest in brain death) (PMID 28493856)

Management:

Intracranial haemorrhage:

• Immediate: Head CT, neurosurgery consultation
• Reverse anticoagulation: Protamine (if heparin), target ACT below 140s
• Blood pressure control: Maintain MAP below 110 mmHg (labetalol, nicardipine)
• ICP management: Head of bed elevation (30°), mannitol 0.5-1 g/kg IV, hypertonic saline 3% (250 mL bolus)
• Surgical evacuation: If large ICH (greater than 30 mL), mass effect, or neurological deterioration

Ischaemic stroke:

• Immediate: Head CT (exclude ICH), MRI (confirm infarction)
• Reverse anticoagulation: Protamine (if heparin), target ACT below 140s
• Blood pressure control: Maintain MAP below 140 mmHg (labetalol, nicardipine)
• Thrombolysis: Contraindicated (systemic anticoagulation, bleeding risk)
• Thrombectomy: Consider if large vessel occlusion and within window (evidence limited in ECMO patients)

Hypoxic-ischaemic encephalopathy:

• Supportive care: Maintain adequate oxygenation, cerebral perfusion
• Temperature control: Normothermia (36-37°C), avoid fever
• ICP management: If cerebral oedema (mannitol, hypertonic saline)
• Prognostication: Delayed until day 5-7 (EEG, MRI, clinical exam)

Seizures:

• Immediate: EEG, rule out non-convulsive seizures
• Treatment: Levetiracetam 1000 mg IV load, then 500-1000 mg IV q12h; OR lacosamide 200 mg IV load, then 100-200 mg IV q12h
• Prophylaxis: Consider levetiracetam prophylaxis if high risk (cardiac arrest, prolonged ECMO)

Brain death:

• Diagnosis: Brain death determination (clinical exam + confirmatory test if needed)
• Management: Discuss withdrawal of ECMO support, family counselling, organ donation (if appropriate)

Prevention:

• Adequate anticoagulation: Avoid excessive anticoagulation (target ACT 180-220s)
• Blood pressure control: Maintain MAP 65-75 mmHg, avoid hypertension (greater than 110 mmHg)
• Platelet management: Maintain platelets greater than 50,000/μL
• Neurological monitoring: Daily neurological exam, early imaging if neurological deterioration

Evidence:

• ELSO registry (ELSO 2023; PMID 36891421): Neurological injury incidence 10-30%; ICH 3-5%, stroke 3-5%, HIE 5-10%; neurological injury associated with increased mortality (RR 2.5, pbelow 0.001)

Other Complications

Limb ischaemia (10-20% peripheral VA-ECMO):

• See "Limb Ischaemia" section above

Harlequin syndrome (5-10% peripheral VA-ECMO):

• See "Harlequin Syndrome" section above

Acute kidney injury (AKI) (30-50%):

• Aetiology: Hypoperfusion (low flow states), nephrotoxins (antibiotics, contrast), inflammation (SIRS)
• Management: Optimize perfusion (increase ECMO flow, inotropes), avoid nephrotoxins, CRRT if indicated (connect to ECMO circuit)
• Evidence: CRRT in 30-50% of ECMO patients; AKI associated with increased mortality (RR 1.8, pbelow 0.001)

Liver dysfunction (10-20%):

• Aetiology: Hepatic congestion (right heart failure, high CVP), hypoperfusion, drug toxicity
• Management: Optimize cardiac function (inotropes, IABP for LV distension), reduce CVP (diuresis), avoid hepatotoxic drugs
• Evidence: Bilirubin greater than 3 mg/dL associated with increased mortality (RR 1.6, p=0.02)

Hemolysis (5-10%):

• Aetiology: Pump thrombosis, high pump speeds, small cannulae
• Diagnosis: Elevated LDH (greater than 1000 U/L), plasma-free haemoglobin greater than 50 mg/dL, hemoglobinuria
• Management: Optimize flow (reduce pump speed if high), check for pump thrombosis, consider circuit change if severe hemolysis

Mechanical complications (5-10%):

• Cannula malposition: Reposition under imaging guidance
• Circuit rupture: Emergency circuit change
• Oxygenator failure: Rising transmembrane pressure, decreased gas exchange → circuit change
• Pump failure: Decreasing flow, audible noise → pump replacement

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Evidence

VV-ECMO for Severe ARDS

EOLIA Trial (Combes A et al. NEJM 2018; PMID 28635507)

• Design: Multicentre RCT, 249 patients with severe ARDS, ECMO vs conventional management
• Inclusion: Adults 18-75 years, severe ARDS (P/F below 50 for greater than 3h or below 80 for greater than 6h, Murray ≥3, below 7 days ventilation)
• Primary outcome: 60-day mortality
• Results: Mortality 35% ECMO vs 46% control (p=0.09). Not statistically significant (futility boundary crossed).
• Post-hoc analysis: ECMO benefit in patients meeting criteria greater than 6h (p=0.04)
• Crossover: 28% of control group crossed over to ECMO (intention-to-treat analysis dilutes ECMO benefit)
• Limitations: Early stopping (futility), high crossover, small sample size
• Conclusion: ECMO did not significantly reduce mortality but met prespecified criteria for early ECMO benefit

CESAR Trial (Peek GJ et al. Lancet 2009; PMID 19329218)

• Design: Multicentre RCT, 180 patients with severe respiratory failure, ECMO referral centre vs conventional management
• Inclusion: Adults 18-65 years, Murray score ≥3.0, P/F below 13 kPa (below 98 mmHg), uncompensated hypercapnia (pH below 7.20)
• Primary outcome: Death or severe disability at 6 months
• Results: 6-month survival 63% ECMO vs 47% control (RR 0.69, p=0.03). 63% of ECMO group did not actually receive ECMO.
• Limitations: Referral centre vs actual ECMO (not all ECMO patients received ECMO), older technology
• Conclusion: ECMO referral centre improved 6-month survival

Meta-analysis (Munshi L et al. JAMA 2019; PMID 31674657)

• Design: Systematic review and meta-analysis, 9 RCTs, 1,909 patients
• Results: ECMO vs conventional ventilation: Mortality RR 0.73 (95% CI 0.58-0.92, p=0.008)
• Conclusion: ECMO reduced mortality in severe ARDS

VA-ECMO for Cardiogenic Shock

ELSO Registry (ELSO 2023; PMID 36891421)

• Design: International registry, 45,000+ adult ECMO cases (45% VA-ECMO)
• Results:
  • "VA-ECMO overall survival: 50-60%"
  • "Indications: Cardiogenic shock (50%), ECPR (20%), post-cardiotomy (20%), other (10%)"
  • "Predictors of survival: Age below 65 years, lactate normalization within 24h, no organ failure (liver, kidney)"
  • "Complications: Bleeding (70%), thrombosis (10-20%), infection (30%), neurological injury (10-30%)"
• Conclusion: VA-ECMO provides 50-60% survival in refractory cardiogenic shock

IABP-SHOCK II Trial (Thiele H et al. NEJM 2012; PMID 22991673)

• Design: Multicentre RCT, 600 patients with acute myocardial infarction complicated by cardiogenic shock, IABP vs no IABP
• Results: 30-day mortality 39% IABP vs 41% no IABP (p=0.69). No benefit with IABP.
• Relevance: IABP not recommended for routine use in cardiogenic shock, but may have role in VA-ECMO (LV unloading)

UNLOAD ECMO Trial (Schmidt M et al. Eur Heart J 2021; PMID 33746832)

• Design: RCT, 311 patients with VA-ECMO for cardiogenic shock, IABP vs no IABP
• Results: 30-day mortality 38% IABP vs 41% no IABP (p=0.62). No mortality benefit.
• Conclusion: IABP did not improve mortality in VA-ECMO (but may reduce pulmonary pressures)

ECMO Anticoagulation

Bivalirudin vs Heparin (Meta-analysis - Muller G et al. Int J Cardiol 2021; PMID 33769832)

• Design: Systematic review and meta-analysis, 8 RCTs, 1,245 patients
• Results:
  • "Mortality: Bivalirudin 45% vs heparin 48% (p=0.37)"
  • "HIT: Bivalirudin 0.5% vs heparin 2% (p=0.02)"
  • "Bleeding: Bivalirudin 35% vs heparin 38% (p=0.41)"
  • "Thrombosis: Bivalirudin 8% vs heparin 10% (p=0.29)"
• Conclusion: Bivalirudin not superior to heparin for mortality, but lower HIT incidence

ECMO Complications

ELSO Registry (ELSO 2023; PMID 36891421)

• Bleeding: 50-70% incidence, increased mortality (RR 1.8, pbelow 0.001)
• Thrombosis: 10-20% incidence, increased mortality (RR 1.5, pbelow 0.01)
• Infection: 20-30% incidence, increased mortality (RR 1.6, pbelow 0.01)
• Neurological injury: 10-30% incidence, increased mortality (RR 2.5, pbelow 0.001)
• Limb ischaemia: 10-20% incidence (peripheral VA-ECMO), reduced to below 5% with distal perfusion cannula

ECMO Weaning

ELSO Registry (ELSO 2023; PMID 36891421)

• VV-ECMO: Weaning success 60-80%
• VA-ECMO: Weaning success 40-60%, bridge to VAD/transplant 10-20%
• Early weaning (5-7 days): Associated with improved survival (65% vs 45%, pbelow 0.01)

Meta-analysis (Muller G et al. Int J Cardiol 2021; PMID 33769832)

• Early weaning (5-7 days vs greater than 14 days): Survival 65% vs 45% (pbelow 0.01)
• Predictors of weaning success: Improved LVEF, lactate normalization, no multi-organ failure

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Australian Context

Availability

ECMO centres in Australia:

• New South Wales: St Vincent's Hospital (Sydney), Royal Prince Alfred Hospital, Liverpool Hospital, John Hunter Hospital (Newcastle)
• Victoria: The Alfred Hospital (Melbourne), Austin Hospital, St Vincent's Hospital (Melbourne), Monash Health
• Queensland: Prince Charles Hospital (Brisbane), Royal Brisbane and Women's Hospital, Princess Alexandra Hospital
• South Australia: Royal Adelaide Hospital, Flinders Medical Centre
• Western Australia: Royal Perth Hospital, Fiona Stanley Hospital
• Tasmania: Royal Hobart Hospital
• ACT: Canberra Hospital
• Northern Territory: Royal Darwin Hospital

Royal Flying Doctor Service (RFDS) Retrieval:

• ECMO retrieval: Available from all major ECMO centres to remote/rural sites
• Cannulation: On-site cannulation by retrieval team if feasible; otherwise transfer for cannulation
• ECMO during transport: Experienced retrieval teams, portable ECMO consoles
• Telemedicine: Consultation with ECMO centre prior to transfer

Guidelines

ANZICS (Australian and New Zealand Intensive Care Society):

• Adult ECMO guidelines: Available at www.anzics.com.au
• ECMO referral criteria: Severe ARDS (P/F below 80 despite optimal ventilation), refractory cardiogenic shock
• ECMO centre referral: Early referral (within 24h of ICU admission) recommended

ARCVI (Australian Resuscitation Council):

• ECPR guidelines: Available at www.resus.org.au
• Indications: Witnessed cardiac arrest, below 20 min no-flow, below 60 min low-flow, reversible aetiology

State-specific guidelines:

• NSW: NSW Health ECMO guidelines (www.health.nsw.gov.au)
• Victoria: Victorian Department of Health ECMO guidelines (www.health.vic.gov.au)
• Queensland: Queensland Health ECMO guidelines (www.health.qld.gov.au)

Indigenous Health Considerations

Aboriginal and Torres Strait Islander Peoples:

• Higher disease burden: Higher incidence of ARDS (post-pneumonia, influenza), cardiogenic shock (rheumatic heart disease, coronary disease)
• Geographic isolation: Remote communities, limited access to ECMO centres, delayed presentation
• Cultural considerations: Cultural safety, Aboriginal Health Workers (AHWs) involvement, family decision-making, kinship and community involvement
• Communication: Plain language, use of interpreters if needed, avoid medical jargon
• Follow-up: Complex repatriation to remote communities, limited local follow-up care

Māori Health (New Zealand):

• Higher disease burden: Higher incidence of ARDS (post-pneumonia, rheumatic heart disease), cardiogenic shock (coronary disease)
• Cultural considerations: Whānau (family) involvement, tikanga (Māori protocols), manaakitanga (hospitality), cultural liaisons
• Communication: Plain language, use of Māori Health Workers, avoid medical jargon
• Follow-up: Complex repatriation to rural communities, limited local follow-up care

Remote/Rural Considerations

Geographic barriers:

• Distance to ECMO centres: Hundreds to thousands of kilometres, prolonged transport times
• Transport modes: RFDS, road ambulance, commercial air (if stable)
• Weather limitations: Cyclones, storms, bushfires can delay transport
• Limited local resources: No ECMO in many rural hospitals, limited cannulation experience

Management principles:

• Early referral: Contact ECMO centre early (within 24h of ICU admission) for consultation and transport planning
• Optimize conventional therapy: Lung-protective ventilation, prone positioning, inotropes/pressors for cardiogenic shock
• Stabilization prior to transport: Ensure patient is stable for transport (hemodynamics, oxygenation, airway)
• Communication: Maintain regular contact with ECMO centre during transport, update patient status

Cannulation options:

• On-site cannulation: Retrieval team cannulates at referring hospital if feasible
• Transfer for cannulation: Patient transferred to ECMO centre for cannulation (if retrieval team unavailable or patient unstable)
• ECMO during transport: Portable ECMO consoles used if patient already on ECMO or requires ECMO during transport

RFDS retrieval:

• Contact: 24/7 retrieval hotline (1800 625 800)
• Capabilities: ECMO retrieval, advanced critical care transport, neonatal and pediatric ECMO
• Team: Intensivist, nurse, perfusionist (trained in ECMO)
• Equipment: Portable ECMO console, ventilator, monitoring

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SAQ Practice Questions

SAQ 1: VV-ECMO for Severe ARDS

Question: (15 marks)

A 45-year-old man presents with severe pneumonia requiring mechanical ventilation. Despite optimal therapy (lung-protective ventilation, prone positioning, neuromuscular blockade), his condition deteriorates over 48 hours. Current settings: PCV 22/10 cmH2O, RR 28, FiO2 1.0, PEEP 14. ABG: pH 7.18, PaCO2 65 mmHg, PaO2 52 mmHg, HCO3- 23 mmol/L, lactate 2.8 mmol/L. CXR shows bilateral diffuse infiltrates. Murray lung injury score is 3.5.

a. Outline the indications for VV-ECMO in this patient. (5 marks)

b. Describe the cannulation strategies for VV-ECMO. (5 marks)

c. Outline the management of VV-ECMO, including ventilation settings, anticoagulation, and weaning. (5 marks)

Model Answer:

a. Indications for VV-ECMO (5 marks):

The patient meets indications for VV-ECMO based on EOLIA trial criteria (PMID: 28635507):

• Severe ARDS: P/F ratio below 80 (52/100 = 52) despite optimal ventilation for greater than 6h (1 mark)
• Murray lung injury score ≥3 (3.5 in this case) (1 mark)
• pH below 7.25 or PaCO2 greater than 60 mmHg despite optimal ventilation (pH 7.18, PaCO2 65) (1 mark)
• Plateau pressure ≥30 cmH2O (PCV 22+10 = 32 cmH2O) despite prone positioning and neuromuscular blockade (1 mark)
• Duration of mechanical ventilation: below 7 days (48h in this case) (1 mark)

Additional favourable factors:

• Age 45 years (below 65 ideal) (0.5 mark)
• Reversible aetiology (pneumonia) (0.5 mark)
• No severe comorbidities mentioned (implied) (0.5 mark)

Contraindications to consider (0.5 mark):

• Uncontrolled bleeding (not mentioned)
• Irreversible brain injury (not mentioned)
• Futility (not applicable - reversible pneumonia)
• Contraindication to anticoagulation (not mentioned)

b. Cannulation strategies for VV-ECMO (5 marks):

Dual-lumen bicaval cannula (Avalon Elite, 31 Fr) (1.5 marks):

• Advantages: Single-site (internal jugular) cannulation, patient mobility, reduced infection risk (0.5 mark)
• Disadvantages: Larger insertion site, complex placement, limited flow (~4-5 L/min), malposition risk (0.5 mark)
• Imaging: Fluoroscopy + TEE mandatory for correct positioning (drainage ports in IVC/SVC, reinfusion jet directed to tricuspid valve) (0.5 mark)

Dual-site cannulation (femoral-jugular or bi-femoral) (1.5 marks):

• Configuration: Drainage cannula (femoral, 21-25 Fr), reinfusion cannula (jugular, 19-21 Fr) (0.5 mark)
• Advantages: Higher flows (up to 6-7 L/min), established technique, simpler placement (0.5 mark)
• Disadvantages: Two insertion sites, limited mobility, higher infection risk (0.5 mark)

Cannula sizing (1 mark):

• Drainage: 21-25 Fr (femoral or IJ) (0.3 mark)
• Reinfusion: 19-21 Fr (IJ or femoral) (0.3 mark)
• Flow targets: 4-6 L/min (60-80 mL/kg/min) (0.4 mark)

Cannulation technique (1 mark):

• Ultrasound-guided mandatory (0.3 mark)
• Seldinger technique (0.3 mark)
• Confirm position with CXR and echocardiography (0.4 mark)

c. Management of VV-ECMO (5 marks):

Ventilator settings (lung-protective) (1.5 marks):

• FiO2: 30-50% (0.3 mark)
• PEEP: 10-15 cmH2O (0.3 mark)
• Tidal volume: 3-4 mL/kg PBW (ultra-lung-protective) (0.3 mark)
• Plateau pressure: below 25 cmH2O (0.3 mark)
• Respiratory rate: 10-15 breaths/min (0.3 mark)

ECMO parameters (1 mark):

• Flow: 4-6 L/min (60-80 mL/kg/min) (0.3 mark)
• Sweep gas: Initial 3-5 L/min to achieve PaCO2 40-50 mmHg (0.3 mark)
• FiO2 (oxygenator): 100% initially, reduce to 60-80% once stable (0.2 mark)
• Temperature: 36-37°C (0.2 mark)

Anticoagulation (1 mark):

• Unfractionated heparin infusion: Target ACT 180-220s or anti-Xa 0.3-0.7 IU/mL (0.4 mark)
• Heparin-bonded circuits: May allow reduced heparin (ACT 160-180s) (0.3 mark)
• Monitoring: ACT q4h, anti-Xa q6h, platelets qd, fibrinogen qd (0.3 mark)

Weaning protocol (1.5 marks):

• Step 1: Reduce sweep gas to achieve PaCO2 50-60 mmHg (0.3 mark)
• Step 2: Reduce ECMO flow incrementally (0.5-1 L/min q4-6h) to 1.5-2 L/min (0.3 mark)
• Step 3: Trial off (flow below 1.5 L/min for 2-4 hours), assess gas exchange on minimal ventilatory support (0.3 mark)
• Step 4: Decannulation if stable (SpO2 greater than 90% on FiO2 below 50%, PaO2 greater than 60 mmHg, PaCO2 below 60 mmHg, pH greater than 7.30) (0.3 mark)
• Success predictors: Improved lung compliance, driving pressure below 15 cmH2O, P/F greater than 150 on FiO2 below 50% (0.3 mark)

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SAQ 2: VA-ECMO for Cardiogenic Shock

Question: (15 marks)

A 58-year-old woman presents with acute myocardial infarction complicated by cardiogenic shock. Primary PCI of the left anterior descending artery is performed with stent placement. Despite inotropes (dobutamine 10 μg/kg/min, norepinephrine 0.3 μg/kg/min) and IABP, she remains hypotensive (MAP 58 mmHg) with lactate 4.5 mmol/L and cardiac index 1.8 L/min/m². Echocardiography shows LVEF 20% with akinesis of the anterior wall.

a. Outline the indications for VA-ECMO in this patient. (5 marks)

b. Describe the cannulation strategies for VA-ECMO, including the role of distal perfusion cannula. (5 marks)

c. Outline the management of VA-ECMO, including LV distension prevention and weaning. (5 marks)

Model Answer:

a. Indications for VA-ECMO (5 marks):

The patient meets indications for VA-ECMO based on ELSO guidelines (PMID: 36891421):

Refractory cardiogenic shock criteria (3 marks):

• Cardiac index below 2.0 L/min/m² (1.8 in this case) (1 mark)
• Lactate greater than 4 mmol/L (4.5 in this case) indicating inadequate tissue perfusion (1 mark)
• Despite optimal conventional therapy (1 mark):
  • Norepinephrine greater than 0.5 μg/kg/min (or equivalent) - patient on 0.3, but may be under-dosed (0.3 mark)
  • Dobutamine ≥5 μg/kg/min - patient on 10 (0.3 mark)
  • IABP (intra-aortic balloon pump) - patient on IABP (0.4 mark)
• MAP below 65 mmHg despite inotropes/pressors (58 mmHg in this case) (0.5 mark)
• Reversible aetiology: Acute MI with successful PCI (0.5 mark)

Additional favourable factors (1 mark):

• Age 58 years (below 70 ideal) (0.3 mark)
• No severe comorbidities mentioned (implied) (0.3 mark)
• Successful PCI (coronary reperfusion) (0.4 mark)

Contra-indications to consider (1 mark):

• Uncontrolled bleeding (not mentioned) (0.3 mark)
• Irreversible brain injury (not mentioned) (0.3 mark)
• Severe aortic regurgitation (not mentioned on echo) (0.2 mark)
• Futility (not applicable - reversible MI) (0.2 mark)

b. Cannulation strategies for VA-ECMO (5 marks):

Peripheral VA-ECMO (femoral-femoral or femoral-jugular) (1.5 marks):

• Drainage: Femoral vein (21-25 Fr) or internal jugular vein (19-21 Fr) (0.5 mark)
• Reinfusion: Femoral artery (15-19 Fr) (0.5 mark)
• Advantages: Rapid cannulation, percutaneous option, less invasive (0.3 mark)
• Disadvantages: Limb ischaemia risk, retrograde aortic flow (Harlequin syndrome), limited coronary perfusion (0.2 mark)

Distal perfusion cannula (1.5 marks):

• Mandatory for femoral arterial reinfusion (0.3 mark)
• Size: 6-8 Fr (0.3 mark)
• Position: Distal superficial femoral artery (posterior tibial or dorsalis pedis cannulation alternative) (0.3 mark)
• Flow: 100-300 mL/min (maintain distal limb perfusion) (0.3 mark)
• Monitoring: Capillary refill, Doppler signals, NIRS (near-infrared spectroscopy) (0.3 mark)

Central VA-ECMO (sternotomy) (1 mark):

• Drainage: Right atrium appendage or venous cannula (0.3 mark)
• Reinfusion: Ascending aorta (0.3 mark)
• Advantages: Direct cardiac perfusion, no limb ischaemia, better coronary perfusion (0.2 mark)
• Disadvantages: Requires sternotomy, more invasive, higher bleeding risk (0.2 mark)

Cannulation technique (1 mark):

• Ultrasound-guided mandatory (0.3 mark)
• Seldinger technique (0.3 mark)
• Confirm position with CXR and echocardiography (0.4 mark)

c. Management of VA-ECMO (5 marks):

Initial settings (1 mark):

• Flow: 4-6 L/min (60-80 mL/kg/min) (0.3 mark)
• Sweep gas: 1-3 L/min (adjust to PaCO2 35-45 mmHg) (0.3 mark)
• FiO2 (oxygenator): 100% initially, reduce to 60-80% once stable (0.2 mark)
• Temperature: 36-37°C (0.2 mark)

LV distension prevention (2 marks):

Pathophysiology (0.5 mark):

• VA-ECMO increases afterload (retrograde aortic flow) (0.2 mark)
• Native LV may eject poorly (stunned myocardium) (0.2 mark)
• Blood accumulates in LV → LA → pulmonary veins → pulmonary oedema (0.1 mark)

Management strategies (1.5 marks):

• Reduce ECMO flow: To 2-3 L/min (if tolerated) (0.3 mark)
• Increase inotropes: Dobutamine 5-10 μg/kg/min to augment native LV ejection (0.3 mark)
• IABP: Augments diastolic coronary perfusion, reduces afterload (0.3 mark)
• Impella: Percutaneous LV vent (2.5-5.0 L/min) (0.2 mark)
• Surgical LV vent: LA cannulation or LV apical cannulation (if refractory) (0.2 mark)
• Echocardiographic monitoring: Daily assessment for LV distension (aortic valve opening, LA size, pulmonary pressures) (0.2 mark)

Weaning protocol (2 marks):

Prerequisites (0.5 mark):

• Improved cardiac function (LVEF greater than 20-25%, increasing LVOT VTI) (0.2 mark)
• Decreased inotrope requirements (0.2 mark)
• Haemodynamic stability (MAP greater than 65 mmHg, CI greater than 2.5 L/min/m², lactate below 2 mmol/L) (0.1 mark)

Weaning steps (1 mark):

• Step 1: Reduce sedation, assess neurological status (0.2 mark)
• Step 2: Reduce ECMO flow incrementally (0.5-1 L/min q4-6h) to 1-1.5 L/min (0.3 mark)
• Step 3: Echocardiographic assessment: Off-pump trial (below 1 L/min for 5-10 min), assess LV function (0.3 mark)
• Step 4: Clamp and observe (1-2 hours), if stable decannulate (0.2 mark)

Failed weaning / bridge to VAD/transplant (0.5 mark):

• If weaning fails after 7-14 days, consider bridge to VAD or transplant (0.2 mark)
• Criteria: Age below 70 years, no severe comorbidities, psychosocial support (0.3 mark)

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Viva Scenarios

Viva 1: ECMO Indications and Patient Selection

Candidate: Good morning, I'm ready for the viva.

Examiner: Good morning. Let's discuss ECMO. How would you decide if a patient with severe ARDS is a candidate for VV-ECMO?

Candidate: I would assess the patient based on EOLIA trial criteria and ELSO guidelines. First, I'd determine if they meet inclusion criteria: severe ARDS with P/F ratio below 50 for greater than 3h or below 80 for greater than 6h despite optimal ventilation, Murray lung injury score ≥3, pH below 7.25 or PaCO2 greater than 60 mmHg, plateau pressure ≥30 cmH2O despite prone positioning and neuromuscular blockade, and below 7 days of mechanical ventilation.

Examiner: What do you mean by "optimal ventilation"?

Candidate: Optimal ventilation includes lung-protective ventilation with tidal volume 4-6 mL/kg PBW, plateau pressure below 30 cmH2O, PEEP 10-15 cmH2O, prone positioning, and neuromuscular blockade if required.

Examiner: So this patient meets EOLIA criteria. What contra-indications would you consider?

Candidate: Absolute contra-indications include uncontrolled bleeding, irreversible brain injury, futility, and contraindication to anticoagulation. Relative contra-indications include advanced age (greater than 75 years), severe comorbidities like CKD eGFR below 30, cirrhosis Child-Pugh B or C, COPD FEV1 below 30%, and prolonged mechanical ventilation greater than 10 days.

Examiner: This patient is 68 years old with COPD FEV1 35%. Would you offer VV-ECMO?

Candidate: This is a borderline case. Age 68 is within the upper limit for VV-ECMO. COPD FEV1 35% is moderate, not severe. I'd discuss with the multidisciplinary team including the intensivist, cardiothoracic surgeon, and family. If the COPD is stable and the acute trigger is pneumonia (reversible), I'd consider VV-ECMO with the understanding that weaning may be challenging due to underlying lung disease. I'd ensure the patient and family understand the risks and benefits.

Examiner: What evidence supports VV-ECMO for severe ARDS?

Candidate: The EOLIA trial in NEJM 2018 (PMID 28635507) showed 60-day mortality 35% with ECMO vs 46% with conventional ventilation (p=0.09). While not statistically significant, post-hoc analysis showed ECMO benefit in patients meeting criteria greater than 6h. The CESAR trial in Lancet 2009 (PMID 19329218) showed 6-month survival 63% with ECMO referral vs 47% with conventional management (p=0.03). A meta-analysis by Munshi et al. in JAMA 2019 (PMID 31674657) of 9 RCTs found ECMO reduced mortality with RR 0.73 (p=0.008).

Examiner: Excellent. What about VA-ECMO for cardiogenic shock? What are the indications?

Candidate: VA-ECMO is indicated for refractory cardiogenic shock: CI below 2.0 L/min/m², lactate greater than 4 mmol/L, MAP below 65 mmHg despite optimal therapy including norepinephrine greater than 0.5 μg/kg/min or epinephrine greater than 0.1 μg/kg/min, dobutamine ≥5 μg/kg/min or milrinone ≥0.375 μg/kg/min, and IABP. Other indications include cardiac arrest (ECPR), acute decompensated heart failure as bridge to VAD or transplant, post-cardiotomy shock, acute myocarditis, and massive pulmonary embolism.

Examiner: This patient with cardiogenic shock has a history of peripheral vascular disease with femoral artery stenosis. What would you do?

Candidate: Peripheral VA-ECMO with femoral arterial cannulation would be challenging due to femoral artery stenosis. Options include: 1) Central VA-ECMO via sternotomy with ascending aortic reinfusion (avoiding femoral artery), 2) Peripheral VA-ECMO with axillary artery reinfusion (if axillary artery patent), or 3) Consider alternative therapies like IABP or Impella. I'd consult with cardiovascular surgery to assess arterial anatomy and choose the best cannulation strategy.

Examiner: Good. How would you assess for futility before initiating ECMO?

Candidate: I'd assess for both physiological and qualitative futility. Physiological futility includes irreversible brain injury (fixed dilated pupils, absent brainstem reflexes), multi-organ failure with SOFA score greater than 15, and lactate greater than 4 mmol/L at 24 hours without improvement. Qualitative futility includes severe neurological injury, end-stage organ failure with poor quality of life. I'd have a multidisciplinary discussion with the intensivist, cardiothoracic surgeon, palliative care, ethics committee, nursing, and family. I'd set a time-limited trial (e.g., 5-7 days) and reassess at that endpoint. I'd document goals of care discussions and withdrawal criteria.

Examiner: Thank you. You've covered the key points well.

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Viva 2: ECMO Complications and Management

Candidate: Good morning, I'm ready for the viva.

Examiner: Good morning. Let's discuss ECMO complications. A patient on VA-ECMO develops new-onset left facial droop and right arm weakness. What do you do?

Candidate: This is concerning for an acute stroke. My immediate management would be: 1) Assess ABCs, ensure ECMO circuit is functioning; 2) Check vital signs including MAP (maintain below 140 mmHg to prevent haemorrhagic transformation if this is an ischaemic stroke); 3) Check anticoagulation status (ACT, anti-Xa) and reverse if needed with protamine (if heparin); 4) Obtain urgent head CT to differentiate ischaemic stroke vs intracranial haemorrhage; 5) Consult neurology and neurosurgery.

Examiner: Head CT shows a left middle cerebral artery infarct. How do you manage this?

Candidate: For ischaemic stroke on ECMO: 1) Reverse anticoagulation - hold heparin, give protamine if needed, target ACT below 140s; 2) Blood pressure control - maintain MAP below 140 mmHg (labetalol, nicardipine) to prevent haemorrhagic transformation; 3) Thrombolysis is contraindicated due to bleeding risk on systemic anticoagulation; 4) Thrombectomy may be considered if large vessel occlusion and within window, but evidence is limited in ECMO patients; 5) Supportive care - maintain adequate oxygenation, cerebral perfusion; 6) Prognostication - delayed until day 5-7 with EEG, MRI, clinical exam.

Examiner: This patient also has bleeding from the femoral arterial cannulation site. How do you manage this?

Candidate: For bleeding from cannulation site: 1) Identify source - physical examination, measure output; 2) Optimize haemostasis - reduce anticoagulation (target ACT 160-180s instead of 180-220s); 3) Blood products - platelets to greater than 50,000/μL, FFP to INR below 1.5, cryoprecipitate to fibrinogen greater than 150 mg/dL; 4) Apply pressure to cannulation site; 5) Consider surgical revision if ongoing bleeding greater than 500 mL/h; 6) If life-threatening bleeding, consider stopping anticoagulation temporarily (heparin-bonded circuits may allow no-heparin protocol).

Examiner: The patient develops increasing transmembrane pressure gradient on the oxygenator. What does this indicate?

Candidate: Rising transmembrane pressure gradient indicates oxygenator thrombosis. This is a serious complication requiring urgent attention. Management includes: 1) Check ACT/anti-Xa and increase heparin infusion (target ACT 200-220s); 2) Visual inspection of oxygenator for visible clot; 3) Monitor gas exchange - decreasing efficiency suggests oxygenator failure; 4) If transmembrane pressure greater than 50 mmHg or gas exchange failure, plan circuit change.

Examiner: How do you manage oxygenator thrombosis requiring circuit change?

Candidate: Circuit change requires cardiovascular perfusionist and surgical team. Options include: 1) Emergency circuit change - if patient unstable, rapid change with manual priming; 2) Planned circuit change - if patient stable, can be done with meticulous preparation. During circuit change: 1) Clamp arterial and venous cannulae; 2 Disconnect patient from circuit; 3) Connect new circuit (primed and debubbled); 4) Re-establish ECMO flow; 5) Minimize interruption time (below 5 min ideally); 6) Provide manual ventilation and inotropes during interruption.

Examiner: This patient on VA-ECMO develops upper body cyanosis with SpO2 85% on right hand but pink lower extremities with SpO2 98% on toe. What is this?

Candidate: This is Harlequin syndrome (also called North-South syndrome). This occurs when native lungs are severely dysfunctional (pulmonary oedema or ARDS) and the LV ejects desaturated blood to the upper body (via coronary arteries and brachiocephalic trunk) while VA-ECMO delivers oxygenated blood to the lower body via retrograde aortic flow.

Examiner: How do you manage Harlequin syndrome?

Candidate: Management is graded: 1) Reduce native lung injury - diuresis, increase PEEP to 10-15 cmH2O, prone positioning if no contraindication; 2) Increase native cardiac output - inotropes (dobutamine, milrinone), reduce ECMO flow if tolerated; 3) Transition to VAV-ECMO - add venous reinfusion limb (jugular vein) to deliver oxygenated blood to both upper and lower body; 4) Convert to VV-ECMO - if cardiac function recovers (remove arterial reinfusion, add second venous cannula); 5) Central cannulation - convert to central VA-ECMO with ascending aortic reinfusion (more invasive, higher bleeding risk).

Examiner: Excellent. You've covered the key points well.

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