CONTENTS
basic management issues
- Circuit parameters
- Low circuit flow & circuit flow arrest
management unique to VV ECMO
management unique to VA ECMO
- Ventilator optimization
- Systemic desaturation
- Hemodynamic targets
- LV distension
- Differential hypoxemia
- Central cannulation
- VA ECMO for RV failure
- Weaning off VA ECMO
hematology of ECMO
- Optimal anticoagulation intensity
- Coagulation monitoring
- Commonly used anticoagulants:
- Specific coagulopathies
- Hemoglobin
other topics
- Pulmonary complications
- Gastrointestinal issues
- AKI (acute kidney injury)
- Neurological complications
- Limb ischemia
- Infection & antimicrobials
- ECMO pharmacology
- ECMO radiology
- ECMO in pregnancy
- Candidacy for ECMO
pump speed (RPM)
RPMs in VV ECMO
- ECMO initiation: Titrate up over 1-5 minutes until the predicted blood flow (BSA*1.8 l/min/m2) is reached (calculator for body surface area: 🧮).
- Subsequent titration: Titrate RPM to the minimum amount of flow that maintains adequate systemic oxygenation.
- Usually this will initially be ~5 L/min.
- ⚠️ Increasing pump flow may increase the recirculation fraction. Thus, beyond a certain pump flow rate, further increases in pump flow may not substantially improve oxygenation.
RPMs in VA ECMO
- ECMO initiation: Then titrate up over 1-5 minutes until the predicted blood flow is reached (BSA* 2.4 l/min/m2, ~4 L/min).
- Subsequent titration:
- Adequate MAP and systemic perfusion.
- Avoidance of left ventricular dilation ⚡️ (e.g., maintenance of adequate pulse pressure).
(The actual number of RPMs will vary between machines.)
V' (ECMO blood flow)
ECMO blood flow in VV ECMO
- If the native lung is not working, an ECMO flow >60% of the estimated cardiac output should be adequate (this will usually maintain a systemic saturation >90%). (38999360) However, if the native lung is providing some oxygenation, then less flow may be required.
- Initially, flow is usually ~5 liters/min (max ~7-8 liters/min).
- Safest range?
- ~3-6 L/min is generally safe (although this may vary depending on equipment and patient factors). (Red Book 6e)
- Higher flows increase the risk of hemolysis.
- Lower flows (<2-3 L/min) increase the risk of thrombosis.
- Flow may be weaned off as the native lungs recover. ⚡️
ECMO blood flow in VA ECMO
- Usual targets:
- LV or biventricular failure: ~80% of cardiac output (~4-5 L/min).
- Isolated RV failure: ~60-80% of cardiac output (3-5 L/min).
- If low, see Low circuit flow
Pven (venous pressure, aka P1)
- This is the pressure before blood enters the pump. It reflects the amount of suction needed to drain central venous blood through the cannula and tubing. Excessively negative pressure can cause hemolysis and damage blood vessels.
- Target a value >-100 mm. (Red book 6e) Excessively negative pressures can cause hemolysis.
causes of excessively negative Pven (aka drainage insufficiency)
- Inadequate pump preload (suggested by tubing chatter):
- Hypovolemia.
- Excessive intrathoracic pressure (evaluate for pneumothorax, reduce the mean airway pressure).
- Excessive intra-abdominal pressure (consider sedation; reposition drainage cannula above the diaphragm).
- Large variations in intrathoracic pressure:
- Coughing.
- Bucking the ventilator
- (Treatment: increase sweep flow to reduce respiratory drive; consider opioid to suppress respiratory drive).
- VA ECMO:
- Native cardiac recovery (the heart and ECMO circuit compete for preload).
- Tamponade may compress the right atrium and impede venous drainage.
- Venous cannula or tubing problem:
- Venous catheter is kinked.
- Catheter is malpositioned.
- Venous catheter clot.
- Cannula too small (consider addition of a second drainage cannula).
- Excessive pump speed.
management steps could include
- Reduce pump speed:
- Is it possible to sufficiently support the patient with a lower flow rate?
- Sometimes if there is excessive suction on the access site, reducing pump speed may have a neutral or positive effect on ECMO flow. (Maybauer 2022)
- Assess hemodynamics and etiologies of drainage insufficiency.
- Last resort: placement of an additional drainage catheter.
Pint (internal pressure, aka P2)
- This is the highest pressure in the ECMO circuit.
- It reflects the pressure required to push blood through the membrane, the tubing, and back into the body.
- Goal value is <300 mm to avoid hemolysis (although hemolysis may occur at pressures >250 mm).
Part (arterial pressure, aka post-membrane pressure, aka P3)
- This is the pressure inside the arterial return tubing, after leaving the membrane. It reflects the amount of pressure required to push blood through the arterial tubing, the cannula, and into the body.
- Very high Part (e.g., >300 mm) can cause hemolysis.
return obstruction (high Part, high Pint, stable deltaP)
- High return cannula resistance:
- Catheter is kinked or externally compressed.
- Return cannula is incorrectly positioned (including aortic dissection, in the case of VA ECMO).
- Catheter is clotted (consider increased anticoagulation).
- Catheter size is too small (consider upsizing).
- Increased pressure within the vessel:
- VV ECMO: Central venous pressure is elevated due to tension pneumothorax or pericardial tamponade.
- VA ECMO: Systemic arterial hypertension (MAP >>65 mm).
management of return failure
- Check circuit for any kinks or external pressure on the cannula.
- Evaluate for problems listed above.
- Vascular imaging may be needed.
▵P (transmembrane pressure)
- ▵P = Pint – Part.
- ▵P is normally below ~40-50 mm. (31632747, 24977195, Schmidt 2022)
- ▵P >60 mm and/or consistently rising ▵P without increased circuit flow suggests membrane lung dysfunction. ⚡️
- ▵P >100 mm strongly suggests membrane lung dysfunction. ⚡️ (31632747)
sweep gas flow rate
basics
- Typical range is 1-9 L/min. (33965970)
- Sweep rate affects CO2 clearance. Sweep doesn't affect oxygenation unless the sweep is very low (e.g., <0.5 L/min).
initial sweep flow & pCO2 management
- The initial sweep is usually set at ~50-100% of the ECMO flow rate. (Red Book 6e) Historically, the sweep speed was often set equal to the ECMO flow rate. However, newer membrane oxygenators are increasingly efficient, so starting the sweep flow at at 50% of the ECMO flow may be better.
- Indications to start at a relatively lower sweep speed include:
- [1] Baseline hypercapnia.
- [2] Situations where hypocapnia would be especially detrimental (e.g., elevated intracranial pressure).
- ⚠️ Among patients with baseline hypercapnia, avoid abruptly dropping the pCO2 (which is associated with neurological injury). Hypercapnia may be gradually controlled (e.g., over ~8-12 hours, depending on whether hypercapnia seems to be causing harm, such as right ventricular failure). (Red Book 6e; Maybauer 2022)
subsequent titration of sweep flow is based on:
- [1] Patient comfort: For patients with high respiratory drive and ventilator dyssynchrony, increasing the sweep speed to reduce PaCO2 will reduce the respiratory drive. (Red Book 6e) This may be used to decrease opioid and sedative medication requirements.
- [2] PaCO2 (e.g., targeting a safe pH). The sweep flow rate is inversely proportional to the PaCO2 level, as indicated by the below equation. (Red book 6e)
- ⚠️ For patients on lung rest settings, a low pCO2 may facilitate patient comfort and reduce the work of breathing (as discussed above). Consequently, if a patient is comfortable with a mildly low pCO2 (e.g., 30 mm), this may be fine. (Schmidt 2022) However, note that in the presence of elevated intracranial pressure, a normal pCO2 may be desirable to promote adequate brain perfusion.
(New sweep) = (Current sweep)(Current CO2/Desired CO2)
weaning off VV ECMO
- As the lungs recover, PaCO2 may start to decrease, allowing sweep flow to be decreased.
- If the sweep is <1 L/min, this indicates that native lungs are eliminating nearly all of the CO2.
FdO2 (fraction of delivered O2), aka FsO2 (fraction of sweep gas O2)
VV ECMO
- FdO2 is generally set to 100%.
VA ECMO
- Unlike VV ECMO, blood is delivered directly to the tissues. This creates a risk of tissue hyperoxia.
- Adjust FdO2 to target slight hyperoxemia (PaO2 ~150 mm) after the oxygenator. (34339398)
SarO2 (arterial return saturation) & ParO2 (pO2 in arterial return)
VV ECMO
- SarO2 should be ~100%.
- ParO2 should be >600 mm with a new gas exchange device. ParO2 will decrease over time, but it should remain above ~250 mm (<150-200 mm is abnormally low; see possible causes listed below). (Schmidt 2022)
VA ECMO
- SarO2 should be close to 100% with a ParO2 that is adequate, but not markedly hyperoxic (see the section above regarding FdO2).
- ParO2 should be >2-5 times the FdO2 (e.g., if the FdO2 is 30% then the ParO2 should be >60-150 mm). (Red Book 6e)
causes of low SarO2 & low ParO2
- FdO2 is set too low (FdO2 is discussed in the section above).
- Expected limitation of the membrane lung may occur if SvdO2 is <60% and the flow rate is high (near the rated flow of the membrane lung). (Red Book 6e)
- Membrane lung dysfunction. ⚡️
SvdO2 (venous drainage oxygen saturation), aka SpreO2 (premembrane saturation)
SvdO2 interpretation
- VV ECMO:
- Recirculation may cause rising SvdO2 with a falling systemic oxygen saturation (SaO2).
- SvdO2 >75% suggests recirculation. (Maybauer 2022)
- Shock (low DO2/VO2) may cause falling SvdO2.
- SvdO2 <60% suggests inadequate oxygen delivery. (Red book 6e)
- Recirculation may cause rising SvdO2 with a falling systemic oxygen saturation (SaO2).
- VA ECMO:
- SvdO2 is a more accurate reflection of the mixed venous oxygenation in VA ECMO than in VV ECMO (since recirculation isn't possible with VA ECMO).
- SvdO2 should ideally be >65-70%. (Red book 6e; 65% Choi 2019 31364329)
- Interpretation should involve integration of the SvdO2 value with other signs of perfusion (e.g., urine output, skin perfusion).
causes of low SvdO2
- Systemic hypoxemia.
- Shock.
- Anemia.
- Increased oxygen consumption (e.g., fever, shivering).
management of low SvdO2 may include
- Management of systemic hypoxemia (if present).
- Increase systemic blood flow:
- VV ECMO: If cardiogenic shock has developed, treat it (e.g., addition of an inotrope).
- VA ECMO:
- Increase ECMO flow as able.
- Reduce afterload if excessive.
- Reduce oxygen consumption: (34339398)
- Treat fever.
- Treat shivering. 📖
- Treat agitation.
- Treat tachypnea / ventilator dyssynchrony:
- Increasing the sweep speed may decrease PaCO2 and thereby reduce the respiratory drive. (Red Book 6e)
- Deepen sedation (and possibly even use paralysis if necessary).
- If all other causes & therapies for hypoxemia have been exhausted, mild hypothermia may be considered (e.g., 36C). (33965970)
- PRBC transfusion may be considered (although efficacy is unclear; discussed further here: ⚡️).
causes of low circuit flow
- Preload inadequate (low Pven): ⚡️
- Membrane failure (elevated ▵P): ⚡️
- Afterload excessive (high Part, high Pint, stable deltaP): ⚡️
- Inadequate RPMs.
circuit flow arrest
- [1] Clamp still on (shortly after circuit initiation, check to ensure all clamps have been removed).
- [2] Pump failure (mechanical or electrical).
- [3] Catastrophic clot.
- [4] Extra-luminal cannula: Chest radiograph or US to ensure the cannula is in the correct vessel without dissection.
- [5] Arterial air alarm: If the arterial bubble detector senses air, the pump will stop.
- [6] Pump air lock: If the pump has been incompletely primed or has entrained a large amount of air, it will fail.
causes
- Console dysfunction:
- Loss of power.
- Electronic malfunction.
- Driver failure:
- Not coupled with the pump head.
- Pump head failure:
- Thrombosis (noise may be heard).
- Air embolism (pump head airlock).
differential diagnosis
- Flowmeter dysfunction.
clinical presentation
- Abrupt loss of ECMO flow.
management
- Pump head failure:
- Airlock: de-airing.
- Thrombosis: change pump or ECMO circuit.
- Try hand crank or backup console (but not for thrombosis or airlock).
- VA ECMO: clamp the circuit to prevent backwards flow that may cause a large arteriovenous shunt. (Schmidt 2022)
- CPR may be required.
manifestations of membrane lung dysfunction may include:
[1] key finding is elevated ▵P
- ▵P is normally below ~40-50 mm. (31632747, 24977195)
- ▵P >60 mm and/or consistently rising ▵P without increased circuit flow suggests membrane lung dysfunction.
- However, the best parameter to trend is arguably the resistance of the membrane lung (▵P/ECMO blood flow).
- ▵P >100 mm strongly suggests membrane lung dysfunction. (31632747)
- (Other findings may include: High Pint, stable Part, reduced circuit flow.)
[2] hemolysis and/or DIC (discussed below)
[3] impaired gas exchange
- Low SarO2 & low ParO2:
- This suggests membrane dysfunction, if present (discussed further: ⚡️).
- However, clots often reduce the blood flow through the membrane lung, without reducing PaO2 of returning blood (similar to a central pulmonary embolism). (Maybauer 2022)
- Increasing requirement for sweep speed: steadily increasing sweep flow requirements may indicate membrane dysfunction. (Schmidt 2022)
- Reduced oxygen transfer rate (<100-150 ml/min) using the formula below supports the presence of membrane dysfunction. (Red Book 6e; Schmidt 2022) Other oxygenation variables should be maximized prior to calculation (e.g., FsO2 set to 100%). However, it's dubious how much additional insight this calculation adds, beyond simply considering the SarO2 and ParO2. Notably, numerous factors other than membrane lung dysfunction may also cause a reduced oxygen transfer rate (e.g., recirculation, anemia, low ECMO flow).
O2 transfer rate ~ 13.4(ECMO flow)(Hb)(▵ O2 sat)
Example: 13.4(4L/min)(10 mg/dL)(0.30) = 161 ml/min
bedside examination of membrane lung
signs of membrane lung dysfunction
- Visible clots may be present on the membrane. However, this may not correlate well with membrane lung function, since you're seeing only part of the membrane.
- Blood in the arterial tubing isn't bright red.
- Blood leaking across the membrane into the gas exhaust line is another sign of membrane dysfunction – this requires exchange of the membrane. Make sure to keep the gas exhaust outlet vented to the atmosphere until the membrane can be exchanged (otherwise an air embolism may occur). (Schmidt 2022)
basic troubleshooting: ensure that
- Gas source is connected and turned on.
- Blender is set correctly.
- Gas lines are connected and not kinked.
laboratory evaluation of membrane lung function
compare pre- and post-membrane blood gas values
- ⚠️ Sigh the membrane before measuring blood gas values (see below).
- Oxygenation: Post-membrane O2 saturation & pO2 values are discussed here: ⚡️
- Ventilation: Signs of membrane lung dysfunction may include:
- <10 mm difference in pCO2 between pre- and post-membrane blood gas despite an adequate sweep speed.
- Post-membrane pCO2 >45 mm (especially if the sweep gas flow rate is considerably higher than the ECMO flow rate).
hematologic abnormalities:
- DIC: ⚡️
- Rising D-dimer.
- Falling fibrinogen level.
- Prolonged PT and PTT.
- Trends may be more important than individual values. (Maybauer 2022)
- Hemolysis: ⚡️
management of membrane lung dysfunction
- Sighing the lung may improve gas exchange:
- Increase sweep speed to 10-15 liters/minute for 10 seconds.
- This is an attempt to remove any moisture accumulation.
- (This won't eliminate clots in the membrane, so it won't fix an elevated ▵P).
- Increasing anticoagulation levels may stabilize membrane dysfunction. (Schmidt 2022)
- Replace the membrane or entire circuit.
definition
- This refers to any air in the circuit.
causes
- Entrainment: air from the atmosphere.
- [1] Circuit breech pre-pump will suck air from the environment.
- [2] Central or peripheral line near the drainage catheter that is left open or is leaking.
- [3] Drainage cannula partially withdrawn.
- [4] Percutaneous tracheostomy with suction of air through the inferior thyroid vein.
- Cavitation:
- [1] Extremely negative pressure generates microbubbles.
- [2] High sweep gas flow rate with a low blood flow rate.
- Oxygenator:
- Oxygenator membrane rupture.
- Occlusion of gas exhaust outlet. (Schmidt 2022)
manifestation
- Bubble sensor alarm.
- Air in the pump head may cause a distinctive sound.
- Large amount of air may cause pump airlock, with immediate loss of ECMO support.
management
- Eliminate the source of air.
- De-airing the circuit if possible.
- Exchanging the circuit if necessary.
- Patient should be placed in the Trendelenburg position, so that any embolized air will be directed towards the legs. (Schmidt 2022)
basics
- Circuit disruption downstream of the pump will cause blood loss from the circuit.
clinical presentation may include
- Drainage insufficiency.
- Hypotension.
- Flow sensor alarm may be activated.
- Blood leaking out of the circuit.
management
- Place clamps on both sides of disruption, to stop ongoing blood loss.
- Replace or repair the circuit.
- Transfusional support to replace lost blood.
what is the saturation goal?
- Systemic arterial saturation of ~80-90% (PaO2 >~45 mm).
- Target a saturation >80% during rest settings, as long as cardiac output and hemoglobin are adequate. (ELSO guidelines)
- Arterial oxygen saturation is typically ~80-90%. (33965970)
- Venous drainage saturation (SvdO2 ⚡️) of >~60%.
- In the absence of recirculation, SvdO2 may be utilized to assess the adequacy of systemic oxygenation.
- Targeting an SvdO2 >60% is a convenient index of adequate oxygenation. (Red Book 6e)
common causes of systemic desaturation
- Basic system malfunctions (e.g., disconnection of sweep gas tubing).
- Membrane lung dysfunction.
- Recirculation.
- ECMO flow relative insufficiency (<60% of native cardiac output).
- Unusually low SvdO2 saturation.
The approach to systemic desaturation is as follows:
(#1) basic circuit check
- FdO2 is set to 100%.
- Sweep is functioning.
- Tubing is connected correctly.
(#2) evaluate for membrane dysfunction
- Consider ▵P:
- (Further discussion of membrane lung dysfunction : ⚡️)
(#3) evaluate for recirculation
diagnosis: signs of recirculation
- Visualization:
- Blood exiting and entering patient may have a similar color.
- The withdrawal cannula may show flashes of bright red blood. (Schmidt 2022)
- Increased SvdO2 >75%.
- (SpO2 – SvdO2) <10%.
- Paradoxical decrease in systemic saturation may occur with increasing ECMO flow. (33965970)
- Radiography may suggest cannula malposition:
- If two cannulas are used: Placement within <8-10 cm suggests recirculation.
- If a double-lumen cannula is used: Placement with the arterial outflow pointing away from the right atrium may promote recirculation.
management of recirculation
- Changing the ratio of circuit flow / cardiac output:
- Increasing the native cardiac output will reduce recirculation.
- Reducing pump speed will reduce the recirculation fraction (but this won't necessarily improve systemic oxygenation).
- Reposition catheter(s) if malpositioned:
- With a dual lumen catheter (e.g. Avalon) – make sure return port is oriented towards the tricuspid valve. POCUS or TEE may be helpful. (Maybauer 2022) Also ensure that the catheter hasn't been malpositioned into the hepatic vein, which may promote recirculation. (Schmidt 2022)
- With two single-lumen catheters, target a separation distance of ~15 cm. (31632747)
- Alter the ECMO circuit:
- Add another venous drainage catheter.
- Switch to a dual-lumen cannula (if feasible).
(#4) is ECMO flow inadequate?
general
- Initially, ECMO flow should be >60% of cardiac output.
- Causes of inadequate ECMO flow:
- Circuit dysfunction.
- Elevated cardiac output.
treatment: increase ECMO flow
- See the section above on low circuit flow. ⚡️
- For persistent hypoxemia, consider increasing ECMO flow to as high as ~6-7 liters/minute if possible. (31632747) However, increased ECMO flow may increase the risk of hemolysis, so this will need to be monitored more carefully at higher flow rates.
(#5) consider measures to increase SvdO2 (especially if SvdO2 is unusually low)
Some venous blood will always bypass the ECMO circuit. Consequently, improving the saturation of the venous blood (SvdO2) will improve the saturation of the systemic arterial blood. Techniques to improve SvdO2 are discussed above: ⚡️
(#6) consider native lung deterioration
diagnosis
- Chest radiograph shows pulmonary deterioration.
- Impaired ventilator mechanics.
management may involve
- Discontinue systemic vasodilators.
- Add inhaled pulmonary vasodilators.
- Increased FiO2 and potentially PEEP:
- Lung rest is ideal, but moderate increases in FiO2 (e.g., 60-70%) are likely safe.
- (With the use of increased sweep speed and low respiratory rates, ventilator-induced lung injury and mechanical power administration to the lung may be kept at a minimum.)
rest ventilator settings (aka ultra-lung-protective ventilation)
general goals for ultra-lung-protective ventilation
- PEEP: ≧10 cm is recommended (10-24 cm is an acceptable range). (33965970)
- Plateau pressure: recommended target is <25 cm (≦ 30 cm is acceptable). (33965970)
- Plateau <20 cm may be associated with less ventilator-induced lung injury and improved outcomes. (33965970)
- Tidal volume ~4 cc/kg ideal body weight.
- Driving pressure <14 cm.
- Respiratory rate: recommended target is 4-15. (33965970)
- CO2 clearance can be easily achieved with sweep flow, so minute ventilation should be minimized to reduce mechanical power delivery to the lungs.
- Note that reducing the respiratory rate will cause a linear reduction in mechanical power delivered to the lungs. (34597688)
- Low FiO2: It is recommended to keep FiO2 as low as possible (acceptable range 30-50%). (33965970) Unfortunately the risk of oxygen toxicity at higher FiO2 (e.g., 60-70%) is unclear, so it's unclear how important this target is to achieve.
examples of typical resting settings
- Pressure Control:
- Respiratory rate 10.
- Inspiratory pressure 10 cm, PEEP 10 cm.
- FiO2 40%. (CESAR trial)
- Volume cycled ventilation:
- Respiratory rate 10.
- Tidal volume 4 cc/kg (target plateau ≦24 cm), PEEP ≧10 cm.
- FiO2 40% (range 30-50%). (EOLIA trial)
- APRV: P-Hi 15 cm, T-hi 6 seconds, T-low 0.3 seconds, FiO2 40%.
readiness for weaning
general signs of lung recovery
- Reversal of the process that required ECMO initiation.
- Improved chest radiograph.
- Improved gas exchange:
- Increased etCO2, decreased PaCO2, and perhaps most importantly decreased (etCO2 – PaCO2) gap (this gap reflects the amount of dead space).
- Improved systemic oxygen saturation.
- Increased lung compliance.
criteria for initiating a weaning trial among intubated patients
- Oxygenation:
- FiO2 consistently ≦60%.
- PEEP ≦10 cm.
- PaO2 ≧70 mm.
- Ventilation:
- Tidal volume ≦6 ml/kg IBW.
- Plateau pressure ≦28 cm.
- Respiratory rate ≦28.
- ABG shows that both pH and PaCO2 are acceptable without excessive work of breathing.
- Imaging: Chest radiograph improved.
weaning from VV ECMO
Weaning may occur over a period of several hours to days, based on the patient's condition.
[0] Gradual increase in the level of ventilator support
- During weaning, the ventilator should be gradually liberalized up to a standard, lung-protective level of ventilator support. For example:
- FiO2 may be increased to 30-60%.
- Liberalize respiratory rate to a usual rate (<30 b/min).
- Pressure-regulated modes of ventilation: (33965970)
- Liberalize total pressure to no more than 28 cm.
- Ensure that tidal volumes increase to 6-8 cc/kg.
- Volume-regulated modes of ventilation: (33965970)
- Liberalize tidal volume by 1 cc/kg increments up to 6-8 cc/kg. (Red Book 6e)
- Plateau pressure should be kept ≦28 cm.
- ⚠️ Monitor for excessive work of breathing.
[1] Reduce ECMO blood flow to a moderate level
- 2-3 liters/min might be reasonable.
- Flow should be maintained >1 liter/minute to avoid thrombosis. (33965970)
[2] Reduce sweep gas
- Stepwise reduction in sweep gas flow rate by 0.5-1 L/min to goal of 1 L/min.
- Check ABG with each decrement in sweep gas flow rate.
- Monitor saturation, pH, and work of breathing. (33965970)
[3] Off sweep gas challenge
- Turn off the sweep gas completely for at least 2 hours (ranging from 2-24 hours). (Red book 6e) The gas tubes should be clamped, to prevent oxygen entrainment. (Maybauer 2022) In a series of 192 off-sweep challenges, no significant changes were detected after two hours – so two hours may be an adequate duration. (31736407)
- Oxygen within the membrane lung may be consumed within ~20 minutes, so close attention should be paid to look for delayed desaturation. (Maybauer 2022)
- Pay close attention to:
[4] Decannulation
- Confirm that off-sweep gas ABG shows PaO2 >70 mm and acceptable pH without excessive work of breathing.
- Patient should be NPO (or, if gastric tube is in situ, it should be placed on suction).
- Coagulation & hematology:
- Consider coagulation status (e.g., platelet count, coagulation studies).
- Hold heparin before decannulation (guidelines recommend at least 30-60 minutes).
- Patient should have an active type-&-screen in case there is hemorrhage.
- Decannulate:
- Extreme care is required to avoid air embolism (which may occur if air is entrained through the side holes of a cannula during removal). Short-term paralysis on the ventilator may be used to ensure positive intrathoracic pressure while cannulas are removed. (Maybauer 2022)
- Observe for potential complications:
- Air embolism.
- Pulmonary embolism.
- Bleeding.
- Post-decannulation SIRS.
- Check for DVT after 24 hours. (33965970)
- Risk of DVT may be >60%. Risk factors include femoral site, larger cannula size, and less intense anticoagulation. (Red Book 6e)
basics
- RV dysfunction is common in ARDS (with a rate of ~10-25%).
- VV ECMO may indirectly improve RV dysfunction in several ways:
- Reduced intrathoracic pressures.
- Improved oxygenation.
- Improved pCO2 and pH.
- Patients with severe, chronic pulmonary hypertension may require VA ECMO. However, patients with acute RV dysfunction due to ARDS can generally be managed with VV ECMO.
management of RV dysfunction
- Other treatments for RV dysfunction:
- Pulmonary vasodilators.
- Inotropes.
- Diuretics.
- VA ECMO as a last resort:
- Most RV dysfunction can be managed with VV ECMO, which typically produces fewer complications. (31632747)
- For persistent RV dysfunction, may convert to VVA ECMO.
[#1/2] if the left ventricle is ejecting a significant volume of blood (most patients)
In this scenario, blood from the native lungs will supply the right arm and upper body. Blood from the ECMO circuit will supply the lower body.
ventilator settings regarding oxygenation
- Adjust PEEP and FiO2 to achieve an adequate PaO2 in the right arm.
- PaO2 in the right arm should be <120 mm to reduce the risk of cerebral hyperoxia. (Red Book 6e)
- PEEP:
- PEEP may help prevent left ventricular dilation and cardiogenic pulmonary edema (discussed further: ⚡️). However, high levels of PEEP may worsen right ventricular function and impair venous return (thereby reducing renal perfusion).
- Moderate PEEP is often utilized initially (e.g., 8-10 cm). (Red Book 6e)
ventilator settings regarding ventilation (CO2)
- CO2 clearance will occur via both the membrane lung and the native lungs. This may lead to differential CO2 levels within the body (analogous to differential hypoxemia aka north-south syndrome). However, CO2 differences between venous and arterial blood are much smaller than pO2 differences between venous and arterial blood (e.g., ▵pO2 between arterial and venous blood is often ~75 mm, whereas the ▵pCO2 may be closer to ~5 mm). Consequently, differential CO2 levels are much less consequential than differential O2 levels. An exception to this is that if blood flow through the lungs is extremely sluggish, then blood may be over-ventilated in the lungs, leading to hypocarbia in blood ejected through the aorta.
- The patient's pCO2 and pH values may be optimized via adjusting the patient's minute ventilation and/or adjusting the sweep speed. Predominantly clearing CO2 via the ECMO circuit may promote lung rest, as discussed next.
partial lung rest with VA ECMO
- Since oxygenation of the upper body is dependent on the native lungs, it's not possible to achieve ultra-lung protective ventilation settings as utilized in VV ECMO. However, substantial lung rest is possible with VA ECMO, as follows:
- [1] PEEP and FiO2 are titrated as described above.
- [2] The respiratory rate is decreased to ~6-10 breaths/minute and the tidal volume is reduced to ~6 cc/kg. Remember that reducing the respiratory rate causes a linear reduction in mechanical power delivered to the lungs. (34597688)
- [3] Sweep gas speed in the ECMO circuit is increased, to provide adequate CO2 clearance. Titrate the sweep gas rate to achieve a normal pCO2 in blood returning from the ECMO circuit. Most of the CO2 clearance should occur extracorporeally. (Red Book 6e)
[#2/2] if the body is being supplied primarily by the ECMO circuit (central cannulation)
- This may occur in patients with central cannulation.
- In this situation, oxygenation and ventilation are predominantly performed by the ECMO membrane. ECMO settings may be titrated based on the right arm blood gas values.
- Ventilator settings won't affect systemic tissues much. For patients with concomitant ARDS, it may be desirable to rest the lungs using ultra-lung-protective ventilation similarly to VV ECMO (as discussed above ⚡️).
- [1] Make sure FdO2 is set to 100% and sweep is functioning.
- [2] Is there differential hypoxemia? If so see this section: ⚡️
- [3] If saturation is low everywhere, consider membrane lung dysfunction: ⚡️
MAP goal
- The optimal MAP varies between patients (there is no single optimal MAP).
- Inadequate MAP threatens to cause hypoperfusion and acute kidney injury.
- Excessive MAP may increase LV afterload, causing LV dilation. Alternatively, higher MAPs may be OK for patients with isolated RV dysfunction.
- Most authors suggest targeting a normal MAP (~65-80 mm). (31219839) However, lower MAPs may be acceptable in the context of intact perfusion, especially among patients with chronic hypotension.
hypotension in VA ECMO
MAP = (Native cardiac output + ECMO flow)(SVR)
- [1] Ensure perfusing rhythm.
- [2] Assess volume status and hemoglobin (give fluid or blood if indicated).
- [3] Attempt to increase ECMO flow (if LV distension/forward flow allows).
- [4] Assess SVR (if low, then increase vasopressors).
- [5] If ejection function is decreased on echocardiography, an increased dose of inotrope may be considered (this may be required in tandem with increased ECMO flow, to allow the LV to continue ejecting).
Related topic: low pre-membrane oxygen saturation is discussed here ⚡️
hypertension in VA ECMO
- Assess volume status; diurese if indicated.
- Assess SVR; if high then reduce vasopressor.
- If improved ventricular function on echocardiography:
- Reduce inotrope dose.
- Consider reduction in ECMO flow.
general concept of LV distension
- ECMO increases the MAP. This is good for systemic perfusion, but it increases afterload on the left ventricle.
- If the LV is unable to eject blood against this afterload, this causes a host of problems:
- [1] Left ventricle dilates, pushing it off the Starling Curve.
- [2] Dilation increases the wall tension in the left ventricle, promoting myocardial ischemia.
- [3] Stasis promotes clot formation in LV (even despite full anticoagulation). This may be especially problematic among patients being anticoagulated with bivalirudin (bivalirudin is degraded by serum proteases, so if there is a high degree of stasis this may lead to low local concentrations of bivalirudin).
- [4] Blood backup leads to cardiogenic pulmonary edema, leading to diffuse alveolar hemorrhage. This may also promote the development of pulmonary hypertension. (31530454)
- [6] Sluggish blood flow through the lungs may cause blood exiting the aorta to be over-ventilated (with a low pCO2 and respiratory alkalosis).
- If LV distension occurs with aortic regurgitation, this can be especially problematic (with marked elevation in LV pressures).
- If untreated, LV distension may prevent the LV from recovering.
risk factors for LV distension
- Baseline LVEF <30%.
- Mitral and/or aortic regurgitation.
- Ventricular tachycardia storm.
- Post-cardiac arrest.
diagnosis of LV distension
- Low pulse pressure, measured via A-line in right arm.
- Ideally the pulse pressure should be >10-15 mm. (31219839) This suggests adequate ejection of blood and forward flow through the heart.
- Pulse pressure <10 mm suggests LV distension with poor function (although low LV preload is also possible; for example, due to right ventricular failure).
- end tidal CO2 <15 mm has a good sensitivity for identifying native cardiac output <1 L/min. (32962727)
- Cardiogenic pulmonary edema:
- Thoracic ultrasonography: Bilateral B-lines.
- Chest radiograph: pulmonary edema.
- Echocardiography:
- [1] LV dilation with profoundly reduced ejection fraction.
- [2] The aortic valve should open at minimum of once every three beats. Less frequent opening of the aortic valve indicates LV distension.
- [3] “Smoke” in the left ventricle may be seen reflecting blood stasis (this indicates a high risk of thrombosis).
- [4] At least moderate mitral regurgitation is usually present. There is a bidirectional relationship between mitral regurgitation and LV dilation. Underlying mitral regurgitation promotes LV dilation, but LV dilation itself can cause functional mitral regurgitation. (Maybauer 2022)
management of LV distension
⚠️ Achieving LV ejection as soon as possible is important to avoid thrombosis within the left ventricle.
basic initial maneuvers
- Ensure a perfusing rhythm (e.g., treat VT or VF if present).
- Ensure adequate anticoagulation – There is very high risk for thrombus formation in the left ventricle. Until LV distension can be resolved, ensure that the patient is fully anticoagulated.
reduce ECMO flow rate
- This might be the most effective noninvasive strategy for treating LV distension. (34339398)
- (Further discussion of ECMO flow: ⚡️)
increased PEEP
- Why this may help:
- [1] PEEP may reduce LV preload, thereby decreasing pulmonary blood flow.
- [2] PEEP may reduce LV afterload.
- [3] PEEP may help prevent cardiogenic pulmonary edema.
vasodilators & inodilators
- Vasodilator therapy (if MAP >65 mm):
- Low MAP may be acceptable if perfusion is adequate.
- If patient is on pressors: Wean vasopressors.
- If patient is not on pressors: Consider arterial vasodilator (e.g., nicardipine) or an inodilator (e.g., milrinone).
- Afterload reduction is a very desirable strategy, because this reduces cardiac work (thereby decreasing myocardial ischemia).
- Inodilator therapy:
- Initiate or up-titrate dobutamine or milrinone (most patients with LV failure will need this). These agents provide both inotropy and vasodilation.
- (Avoid excessive inotropic treatment, as this may increase myocardial work and myocardial ischemia.)
diuresis
- If hypervolemic, diuresis may be attempted.
- However, diuresis is probably the least effective therapy for LV distension. (34339398)
if less invasive therapies fail: LV vent
- IABP:
- May improve ejection & coronary artery perfusion.
- Meta-analyses suggest a benefit from IABP in terms of the ability to wean from ECMO. (31530454)
- ⚠️ Pulsatility may be falsely reassuring among patients who have an IABP. For such patients, aortic valve opening should be assessed with echocardiography. (Red Book 6e)
- Impella:
- Impella may increase hemolysis (already a problem on ECMO) or limb ischemia (if both femoral arteries will be cannulated).
- Surgical cannula placed to drain blood (if centrally cannulated).
- Percutaneous transseptal venting of the left atrium, or balloon atrial septostomy.
epidemiology
- Occurs in ~8% of patients on VA ECMO with peripheral cannulation.
cause
- Three factors all required for differential hypoxemia:
- [1] VA ECMO with an arterial catheter in the femoral position.
- [2] Native cardiac output is sufficient to push the mixing cloud down the aorta.
- [3] Native lungs aren't working.
- (If the IVC is utilized for venous drainage, this may make matters even worse by establishing dual-circuit circulation wherein blood tends to circulate either within the upper body or within the lower body – with relatively little mixing between these areas).
- The initiation of differential hypoxemia may relate to one of the following events:
- [1] Recovery of the left ventricle (in the context of ongoing lung failure).
- [2] Development of lung failure (in the context of ongoing left ventricular ejection of blood into the proximal aorta).
- The net effect of these factors is that deoxygenated blood is delivered to the upper body (including brain and coronary arteries).
clinical findings
- Key finding: saturation & PaO2 in right upper extremity is lower than in the lower extremities.
- Venous drainage oxygen saturation (SvdO2 ⚡️) may be unusually high.
- Ventricular arrhythmias may result from perfusing the heart with deoxygenated blood. (31219839)
- Increased pulsatility in the arterial line tracing may be seen.
possible treatments
- Improve the native lung function, e.g.:
- Increase the FiO2 and PEEP.
- Inhaled pulmonary vasodilators.
- Evaluate and treat any new causes of respiratory failure (e.g., VAP).
- Decrease the ratio of (cardiac output)/(ECMO flow):
- [i] May decrease inotrope dose.
- [ii] May decrease the power of a venting Impella.
- [iii] Beta-blocker may be utilized to reduce endogenous cardiac output if it is excessive (although this raises a question of whether VA ECMO is still required). (Red Book 6e)
- [iv] May increase the ECMO flow.
- ⚠️ These therapies may be used as a temporizing measure to preserve oxygenation to the heart and brain. However, they will lead to left ventricular distension – so this isn't a viable long-term solution.
- Switch modalities or access point:
- If heart has recovered but lungs continue to fail – may switch to VV ECMO.
- If patient remains dependent on VA ECMO for cardiac support, may transition to V-AV ECMO:
- Add a cannula to return oxygenated blood to the SVC.
- This produces a combination of VV ECMO & VA ECMO.
- Benefit: improved cerebral & coronary oxygenation.
- Cost: reduced systemic perfusion (will reduce flow going to body), added complexity, increased likelihood of access complications. Individual flowmeters may be needed for both return catheters to avoid excessive flow return to the venous system.
- May move the arterial return cannula to the axillary artery (although this carries a risk of hyperperfusion).
- May convert to central cannulation of the aorta.
reverse differential hypoxemia
- This rare phenomenon involves hypoxemia of the lower body, with normal saturation in the upper body.
- Three factors are required simultaneously to generate this:
- [1] VA ECMO with arterial catheter in femoral position.
- [2] Heart and lungs are working fairly well.
- [3] Membrane failure causes the SarO2 to be low.
- Management may involve either:
- [1] Replace the membrane.
- [2] Consider whether ECMO is still required. Reverse differential hypoxemia occurs only if there is some function of the native lungs and heart, so it can be a sign that ECMO can be weaned and discontinued.
- This is essentially cardiopulmonary bypass.
- Pulse pressure is generally <10 mm.
- ECMO flow is titrated against a MAP goal (~65-70 mm), usually ~5 L/min.
- ECMO flow = perfusion to body.
- Nearly all patients receive an empiric LV vent.
- There are no problems with differential hypoxemia.
examples include:
- Acute RV failure due to pulmonary embolism.
- Long-standing pulmonary hypertension.
some unique issues encountered:
- LV under-filling (rather than LV over-filling).
- RV failing to eject.
LV under-filling
- Clinical manifestation:
- Low pulse pressure.
- LV under-filled on echo.
- Mechanism: RV failure with inadequate blood delivery to LV
- Management:
- [1] Inhaled pulmonary vasodilators (to decrease RV afterload & improve flow to the LV).
- [2] Inotropes to improve RV contractility.
- [3] Decrease afterload (MAP), as clinically tolerated (e.g., with decreased vasopressors or the addition of a vasodilator).
- [4] Decreasing ECMO flow (this may increase preload on the RV, thereby improving flow through the heart).
- Less ECMO flow is generally needed in isolated RV failure.
RV failing to eject
- Failure of RV to eject is problematic:
- (a) Impairs perfusion & recovery of RV.
- (b) May cause stasis & clots in pulmonary vascular bed – especially in the case of massive pulmonary embolism, this may cause catastrophic clot extension.
- (c) Inability to deliver drugs to pulmonary vasculature.
- Management may include:
- Inhaled pulmonary vasodilators.
- Inotropes to improve RV contractility.
- Intravenous pulmonary vasodilator may be considered.
VA ECMO increases LV afterload (which may impair LV function) and reduces RV preload. Weaning VA ECMO involves reducing ECMO support to determine how the heart will respond to increased RV preload and reduced LV afterload.
signs of recovery
cardiac recovery
- Minimal vasoactive/inotropic support, which is defined as 1-2 of the following:
- ECMO flow decreased to 2-2.5 L/min (with adequate mixed venous or central venous oxygen saturation).
- Increased pulse pressure and ejection fraction on echocardiography (further discussion of favorable echocardiographic parameters below).
pulmonary recovery
- Increased SpO2 on moderate FiO2 (≦60%).
- Chest radiograph improvement.
- Decreased PaCO2 & decreased (PaCO2 – etCO2) gap.
- Increased pulmonary compliance.
weaning of VA ECMO
optimize
- Ventilator settings.
- Fluid balance.
- Cardiac medications.
- Support devices (e.g., IABP, Impella).
slowly reduce blood flow to 1 L/min
- Consider intensifying anticoagulation to prevent thrombosis.
- Drop the flow rate by 0.5 L/min every 10-15 minutes until reaching 1 L/min flow. (Red Book 6e)
- Evaluate hemodynamic and respiratory stability (green criteria below). Ventilatory and hemodynamic support may need to be up-titrated.
- ⚠️ NEVER turn off the sweep flow (unlike weaning from VV-ECMO).
clamp trial
- Evaluate for 3-5 minutes on no support (circuit clamped). Evaluate for the following criteria:
- [1] Stable hemodynamics and perfusion, e.g.:
- MAP >60-65 mm.
- Mixed venous oxygen saturation >65%. (Schmidt 2022)
- CVP ≦10-18 cm. (34339398; Maybauer 2022)
- [2] Stable oxygenation.
- [3] Favorable echocardiographic parameters, such as:
- Aortic VTI >10 cm.
- Mitral annulus tissue Doppler peak systolic velocity >6 cm/s.
- LVEF >~25% (ideally the LV will increase during ECMO weaning, due to reduced afterload and preserved contractile reserve). (34339398, Maybauer 2022)
- Absence of significant RV dilation.
- Absence of severe tricuspid regurgitation. (Red Book 6e)
decannulation
- Decannulate.
- Evaluate for complications:
- Neurovascular monitoring for arterial insufficiency.
- Ultrasound evaluation for DVT or arterial thrombus.
Anticoagulation intensity may be personalized based on the following factors. For example, anti-Xa or PTT targets may be adjusted during an ECMO run.
hemorrhage & hemostatic challenges?
- Hemorrhage: Severity? Adequacy of local hemostasis?
- Recent or pending surgeries/procedures?
evidence of pathological thrombosis?
- History of DVT/PE?
- Evidence of intracardiac thrombosis?
- Fibrin or clot formation in the circuit?
- Elevated ▵P?
the net state of anticoagulation: consider all coagulopathies, including
- Medications (e.g., aspirin, P2Y12 inhibitors).
- Uremic coagulopathy.
- Thrombocytopenia.
VV ECMO versus VA ECMO
- VV ECMO doesn't carry a risk of ischemic stroke or intracardiac thrombosis, so lower intensity of anticoagulation may be used.
- If necessary, anticoagulation can be held for prolonged periods with a flow rate maintained at >2.5-3 L/min. (Red Book 6e)
- However, risks of access-site DVT and PE remain high (even despite anticoagulation).
- VA ECMO patients may require more intense anticoagulation:
- [1] There is a higher risk of systemic embolization such as ischemic stroke (especially if there is stasis of blood within the heart).
- [2] During weaning from VA ECMO, circuit flow is reduced – which increases the risk of thrombosis. (37763010)
flow rate & residence time
- Higher flow rates require less anticoagulation:
- Flow rates <~2 L/min increase the risk of circuit thrombosis.
- If anticoagulation can't be achieved, high flows (e.g., 4-5 L/min) should be used to minimize clot formation within the circuit. (31632747)
- Residence time is the average transit time that blood spends in the ECMO circuit. One study of pediatric ECMO found that circuit lifespan may improve when the PTT/RT ratio is >2.5. (31977350) Thus, a simpler circuit with a faster flow rate may require less intense anticoagulation. (38671589)
- (Further discussion of circuit flow: ⚡️)
duration of ECMO & timing
- During an ECMO run, the circuit may become coated with proteins that tend to prevent thrombosis. Later on during an ECMO run, less anticoagulation may be needed.
routine daily hematological monitoring may include
- CBC (complete blood count).
- Indicator of hemolysis (either plasma free hemoglobin or hemolysis index). ⚡️
- Note that many labs will automatically measure hemolysis index with daily electrolytes.
- Fibrinogen level. ⚡️
- Anti-Xa levels ⚡️ (if used for titration of heparin).
- PTT. ⚡️
- INR. ⚡️
platelet count
thrombocytopenia & platelet dysfunction in ECMO
- Platelet count often falls to <40% normal within a few hours of ECMO initiation.
- ~25% of patients experience a platelet count <50,000. (Red Book 6e)
- Aside from a reduction in platelet count, platelet dysfunction may also occur due to reduced glycoprotein (GP)Ib-alpha and GP-VI levels (receptors for vWF and collagen, respectively).
- Thrombocytopenia seems to be an important risk factor for intracranial hemorrhage. (Red Book 6e)
causes of thrombocytopenia include
- ECMO itself (including: membrane lung dysfunction, pump head thrombosis).
- DIC.
- HIT.
- Other causes of thrombocytopenia in the context of critical illness, e.g.:
- Sepsis.
- Major surgical procedures.
- (Further discussion of causes of thrombocytopenia in ICU: 📖)
platelet transfusion threshold
- Ideal platelet levels are unclear; this may depend on overall balance of hemostasis/thrombosis and clinical context.
- 50 b/L is a commonly utilized transfusion threshold for nonbleeding patients (especially among patients who are on therapeutic anticoagulation), although some protocols have used a target of 30 b/L. (35080509, 38457000)
fibrinogen
- Generally target >~100 mg/dL if no bleeding. (35080509)
- Generally target >150 mg/dL if active hemorrhage. (35080509) However, >200 mg/dL may be targeted in severe hemorrhage, especially in the context of other coagulopathies that are difficult to correct (e.g., thrombocytopenia or antiplatelet agents). (38337414)
- ⚠️ Fibrinogen levels may be measured to be falsely low in patients who are receiving DTIs. (32371744) In that situation, TEG may be preferred (although standard TEG assays don't provide an isolated measurement of fibrinogen level 📖) . (38337414)
D-dimer
- Elevation of D-dimer is nonspecific, but markedly elevated values have greater significance.
- Elevation of D-dimer levels may reflect:
- DIC.
- Clot formation in the pump or oxygenator (suggested by steady increases in D-dimer). (36703184)
INR
- INR correlates poorly with clinical bleeding in the context of complex coagulopathies (e.g., DIC, cirrhosis, sepsis, ECMO).
- Some sources recommend using FFP to “correct” an elevated INR, but there isn't any evidence to support this. (38457000) Consequently, usual algorithms for FFP transfusion in critically ill patients without ECMO may be applied. (38457000) TEG may be helpful to determine if enzymatic coagulation is truly compromised, or whether there is rebalanced enzymatic coagulation.
- ⚠️ INR may be prolonged by DTIs (direct thrombin inhibitors). (36703184)
PTT
uses
- [1] PTT is the primary laboratory test used to titrate DTIs (direct thrombin inhibitors). Unfortunately, PTT may underestimate the true anticoagulant effect of DTIs at higher drug concentrations. (35080509)
- [2] PTT may be used to evaluate the level of UFH (discussed further below).
limitations
- Acute-phase reactants (fibrinogen and factor VIII) may reduce the PTT level, thereby masking the true anticoagulant effect (this generates heparin pseudo-resistance and DTI pseudo-resistance). (35080509)
- Critically ill patients often have baseline PTT elevation due to other coagulopathies (e.g., cirrhosis, DIC). (38671589)
values
- Normal PTT is ~25-35 seconds.
- Target in heparin anticoagulation:
- 50-70 seconds or 2-2.5 times the normal level is recommended by ISTH ECMO guidelines. (36700496)
- 40-60 seconds may be adequate for VV ECMO. (Red Book 6e; recommended target for VV ECMO by Rodriguez et al.; Maybauer 2022)
- >75 seconds may correlate with increased risk of hemorrhage. (31045921)
- Target with direct thrombin inhibitors (bivalirudin, argatroban): The same target ranges may be used as with heparin (listed above). (36700496, Maybauer 2022) For example, ISTH ECMO guidelines recommend targeting 50-70 seconds or 2-2.5 times the normal level with argatroban. (ISTH ECMO guidelines 36700496; 37763010)
anti-Xa level
- This is a specific assay of heparin effect, which is utilized only to titrate unfractionated heparin.
- Anti-Xa level does not represent the overall hemostatic state of the patient. (38671589)
- Falsely low anti-Xa occurs with: (35080509)
- Target anti-Xa level:
TEG (thromboelastography)
basics
- TEG is a whole-blood, integrative assay of coagulation (discussed further here: 📖).
- The TEG R-time is analogous to the PTT, but it is more sensitive to endogenous anticoagulants (allowing it to detect rebalanced hemostasis). Most TEG assays utilize a contact factor activator similar to those utilized in PTT. This causes the R-time to be sensitive to heparins, direct thrombin inhibitors, or deficiencies in the intrinsic coagulation system (VIII, IX, XI, and XII). (36108651)
theoretical advantages of TEG
- TEG may provide a more holistic evaluation of coagulation (including a balance of clotting factors and endogenous anticoagulants – both of which may be depleted during ECMO).
- Comparison of the R-time without heparinase versus with heparinase allows for a direct evaluation of the effect of heparin on coagulation.
evidentiary basis
- One small pilot RCT randomized patients to a PTT-based heparin dosing strategy or titration of heparin to target a TEG-5000 R-time of 16-24 minutes. Clinical outcomes were similar, but as a pilot study these outcomes were underpowered. Patients in the TEG group generally had subtherapeutic anti-Xa levels of 0.1-0.2 IU/ml. Alternatively, patients in the PTT-based heparin titration group had a median R-time of 62 minutes (with 37% of patients having a “flat line” TEG tracing). Among patients with a flat-line TEG tracing, the median anti-Xa level was 0.36 IU/ml. Overall, this study has important implications: (29340875)
- Targeting an R-time of 16-24 likely leads to subtherapeutic anticoagulation.
- TEG-5000 may be excessively sensitive to heparin (with flat-line TEG tracings occurring at therapeutic heparin levels). This casts doubt on whether TEG can be utilized to titrate heparin infusions properly.
unfractionated heparin basics
- Mechanisms of action:
- (a) Potentiates antithrombin, leading to inhibition of factor Xa and thrombin (IIa).
- (b) Binds heparin cofactor II, with the complex inactivating thrombin (IIa).
- (c) Increases release of tissue factor protein inhibitor (TFPI) from the endothelium, which inhibits activation of hemostasis through TF-VIIa
- Clearance: Independent of organ function.
- Half-life: ~60-90 minutes. (35080509)
dosing
- Loading bolus: Generally 75-100 U/kg up to a maximum of 5,000 units. (Red book 6e)
- Maintenance infusion:
- Start the infusion at ~20-25 U/kg/hr initially.
- Range: ~10 to ~70 U/kg/hr (upper limit is discussed in the section below on heparin resistance).
- Infusions should be titrated based on a local heparin protocol.
monitoring of heparin anticoagulation in patients on mechanical support (including patients who only have an Impella)
commonly utilized tests:
- In challenging situations, it might be ideal to check both:
- anti-Xa level ⚡️
- Provides a direct measurement of the heparin effect on coagulation.
- Anti-Xa level may be the best indicator of heparin efficacy. Subtherapeutic anti-Xa levels correlate with clinical thrombosis. (31045921)
- PTT ⚡️
- Evaluates coagulation more globally (including heparin effect and other coagulation factors).
- PTT might be most useful as a global indicator of bleeding risk, rather than an indicator of heparin efficacy. Supratherapeutic PTT levels correlate with clinical bleeding. (31045921)
discordance between anti-Xa and PTT levels
Discordance is common. It is more common for patients to have a disproportionately elevated PTT level, in comparison to the anti-Xa level:
disproportionately elevated PTT (blue boxes above)
- Clinical significance: Elevated PTT levels correlate with increased clinical bleeding risk.
- Potential causes:
- Falsely low anti-Xa levels due to hemolysis, hyperbilirubinemia, or hypertriglyceridemia.
- DIC. Disproportionately elevated PTT levels are associated with concomitant thrombocytopenia and INR prolonged >~1.5. (37954899, 36167522)
- Low fibrinogen level.
- FXI-FXII deficiency due to mechanical support. (This causes an elevated PTT level without excess bleeding risk. In this situation, the PTT may be ignored, with ongoing heparin titration based on anti-Xa level.) (35550692)
- Lupus anticoagulant activity.
- Further investigation:
- Evaluate for underlying causes of coagulopathy (especially DIC).
- Consider that hemolysis, hyperbilirubinemia, or hypertriglyceridemia may artificially lower the anti-Xa level.
- Check the fibrinogen level.
- TEG might be helpful. If TEG demonstrates a normal or reduced R-time, this may suggest that anticoagulation is safe (despite PTT prolongation). (37763010)
- Clinical management?
- Address any underlying etiologies that may be diagnosed and treated (e.g., DIC, hemolysis).
- If fibrinogen levels are below target (e.g., <100 mg/dL), then cryoprecipitate may reduce PTT levels and allow heparin to be given more safely.
- There is no single best treatment for this situation, but the following options may be considered depending on individual patient specifics:
- [1] It might be reasonable to titrate heparin levels based on PTT levels. Anti-Xa levels may be monitored and ideally remain above ~0.2-0.3 IU/ml, depending on the required anticoagulation intensity. (31045921)
- [2] Personalizing anticoagulation targets might be reasonable (e.g., targeting an anti-Xa level of 0.3-0.5 IU/ml rather than 0.3-0.7 IU/ml).
- Address any underlying etiologies that may be diagnosed and treated (e.g., DIC, hemolysis).
disproportionately low PTT level (tan boxes above)
- Clinical significance: Thrombosis seems to correlate more closely with low anti-Xa level (as compared to low PTT level). Thus, patients with a therapeutic anti-Xa level and low PTT level may not be at elevated risk of clinical thrombosis.
- Potential cause: This often reflects heparin pseudo-resistance: Elevated acute-phase reactants (fibrinogen and factor VIII) may reduce the PTT level, thereby masking the true heparin effect. (35080509)
- Clinical management: Titration of heparin based on anti-Xa levels may be most reliable in this scenario.
definition of heparin resistance?
- Definitions of heparin resistance are arbitrary and variable in the literature. (37619694)
- Heparin resistance might be defined as inability to reach therapeutic anticoagulation with a heparin dose of roughly >30 U/kg/hr. (28898902, 37619694)
causes of heparin resistance
- [1] Heparin pseudo-resistance:
- This is a laboratory artefact whereby high levels of fibrinogen and/or Factor VIII artificially reduce the PTT level.
- In heparin pseudo-resistance, anti-Xa levels should remain accurate.
- [2] Heparin level is truly low: This may occur as a response to inflammation, with elevated levels of heparin-binding proteins. Heparin may also bind to the ECMO circuit.
- [3] Antithrombin-III deficiency, which may be caused by:
- DIC.
- Acute thrombosis (e.g., PE, DVT).
- Sepsis.
- Surgery or trauma (antithrombin III levels often nadir ~3 days postoperatively). (29915655)
- ECMO itself, hemodialysis, and possibly IABP. (35927191) ECMO-related AT-III deficiency is frequently seen upon ECMO initiation. (38337414)
- Cirrhosis.
- Unfractionated heparin itself reduces antithrombin levels over time.
- [4] Multifactorial: ECMO patients will usually have many of the above causes of heparin resistance.
investigation of heparin resistance: laboratory studies to obtain
- Three assays of heparin activity should ideally be obtained:
- [1] Anti-Xa level should always be obtained (if it hasn't been already).
- [2] PTT.
- [3] TEG (with and without heparinase).
- Antithrombin-III level (<40% suggests antithrombin-III deficiency may be contributing to heparin resistance).
- INR.
- Fibrinogen and Factor VIII levels (especially if considering transition to direct thrombin inhibitor).
- (PTT with exogenous heparinase: This eliminates the effect of heparin, thereby revealing the baseline PTT value. The exact utility of this test remains unclear, but it might be especially useful in situations where TEG and anti-Xa level are unavailable.)
management of heparin resistance
step #1: If anti-Xa & PTT levels are discordant, consider personalizing the anticoagulation target
- Anti-Xa and PTT levels are frequently discordant. After thoughtfully considering all data (PTT, anti-Xa, TEG, heparin dose, risk of thrombosis/hemorrhage) it may be reasonable to switch to a different assay that seems more appropriate for an individual patient, or personalize the target anticoagulation level. (37519116)
- The approach to discordance between anti-Xa and PTT levels is explored further in the section above on laboratory monitoring of heparin infusions. ⚡️
step #2: Consider simply increasing the heparin dose
- If anti-Xa and PTT levels are both low, this suggests that it's safe to increase the heparin dose.
- Simply increasing the heparin dose may be a simple and inexpensive approach to overcome heparin resistance. The maximal rate of heparin infusion is unknown. Heparin doses of ~40-70 IU/kg/hr may be needed for some patients. (28898902)
- Escalating the heparin dose is especially reasonable if antithrombin-III levels are >40% (implying that the true heparin concentration is low). Alternatively, if antithrombin-III levels are extremely low (<<40%), that may predict a failure of heparin to achieve adequate anticoagulation (in which case transitioning to a direct thrombin inhibitor could be more rapidly effective).
step #3: Consider switching to a DTI (direct thrombin inhibitor)
- Rationale:
- Use of a direct thrombin inhibitor avoids issues relating to heparin resistance due to heparin adsorption to proteins, or antithrombin-III deficiency.
- Direct thrombin inhibitor use in ECMO is supported by numerous studies demonstrating excellent outcomes (mostly with bivalirudin).
- ISTH guidelines recommend switching from heparin to a DTI in patients with treatment failure on heparin. (36700496)
- ⚠️ Caution: DTIs may be subject to pseudo-resistance with PTT monitoring (similarly to heparin). An unexpectedly low PTT level may foreshadow problems here (especially if there is markedly elevated fibrinogen and/or Factor VIII levels). Unfortunately, there is no simple solution to monitoring direct thrombin inhibitors in the context of pseudo-resistance. Please note that patients with heparin pseudo-resistance using PTT are best managed with continuation of a heparin infusion and transitioning to dosing based on anti-Xa levels. Further discussion of DTI pseudo-resistance is here: 📖
(generally not preferred: supplementation of antithrombin-III levels)
- For patients with low antithrombin-III levels, one potential treatment is to administer antithrombin-III concentrate. However, this is often not a preferred strategy for the following reasons:
- [#1] There is little evidentiary basis to support the use of antithrombin-III supplementation for heparin resistance in the ICU (reports are largely limited to case studies).
- [#2] Antithrombin-III is extremely expensive. (24391399)
- [#3] Dosing of antithrombin-III and heparin can be tricky. Heparin and antithrombin-III interact synergistically, so they must be combined carefully.
- [#4] Antithrombin-III supplementation may increase the risk of acute kidney injury. (36853953, 35877927)
- [#5] Many critically ill patients may have multifactorial heparin resistance. Administration of antithrombin-III won't resolve this situation. This may explain a recent RCT that demonstrated that antithrombin supplementation in VV ECMO didn't affect the heparin dose. (32947474)
- [#6] ISTH guidelines don't recommend antithrombin-III supplementation. (36700496)
pharmacokinetics
bivalirudin
- Clearance: 80% is cleared via proteolytic enzymes in the serum, whereas 20% is cleared by the kidneys. (38671589)
- Half-life: 25 minutes with normal renal function (compared to 60-90 minutes for heparin). (35080509) However, in severe renal failure the half-life may increase to an hour.
argatroban
- Clearance: Hepatic (no dose adjustment needed in renal failure).
- Half-life: ~45 minutes (but may increase to 3 hours in patients with severe hepatic dysfunction).
advantages, disadvantages, indications, selection
advantages of DTIs
- [1] No issues with heparin resistance.
- [2] No issues with HIT.
- [3] Pharmacokinetics and pharmacodynamics are often more predictable than those of heparin (due to absence of interaction with antithrombin-III or adsorption to various proteins/surfaces).
- [4] DTIs cause inhibition of both circulating and fibrin-bound thrombin (unlike heparin, which acts only on circulating fibrin). (38671589) This may allow some activity against preformed thrombus. (Maybauer 2022)
- [5] DTIs may cause less thrombocytopenia as compared to heparin (even among patients who don't have HIT, heparin often causes a non-immune mediated thrombocytopenia). (30461625)
- [6] Small, retrospective studies suggest that bivalirudin use associates with reduced risk of bleeding, thrombosis, and in-hospital mortality as compared to heparin (less evidence is available regarding argatroban). (38671589) This is low-quality data, but it does suggest that direct thrombin inhibitor use is safe and effective (whether bivalirudin it truly superior to heparin remains unknown).
disadvantages of DTIs
- [1] No reversal agent (but this is generally unnecessary, given the short half-life of these agents).
- [2] DTIs impair testing of underlying coagulation abnormalities (e.g., DTIs cause abnormalities in the measurement of fibrinogen, INR, and PTT levels).
- [3] Monitoring can be challenging, since this is based entirely on PTT values:
- Patients with elevated fibrinogen and Factor VIII levels may have artificially low PTT levels, causing DTI pseudo-resistance. 📖
- Patients with elevated baseline PTT (e.g., due to cirrhosis or DIC) are at risk of under-dosing if a fixed PTT value is targeted.
- [4] Bivalirudin is metabolized by localized proteolysis. This may lead to subtherapeutic levels in areas of blood stasis (where anticoagulation is most important). This may be especially relevant in the following situations:
- [5] DTIs often have a higher drug acquisition cost as compared to heparin. However, this may be defrayed by a reduction in other costs (e.g., avoidance of supplemental antithrombin-III, fewer circuit changes). Additionally, patients on ECMO often require low doses of DTIs, so dispensing smaller aliquots of drug at a time may reduce drug cost (by avoiding throwing away lots of wasted drug when medication bags dispensed to the ICU expire).
indications for DTIs
- [1] HIT (either suspected or known).
- [2] Heparin resistance.
- [3] Some centers use bivalirudin as a front-line anticoagulant for all ECMO patients.
selection of bivalirudin versus argatroban
- Overall: Bivalirudin has the advantage of a shorter half-life, which allows it to be more easily discontinued for procedures or hemorrhage. However, bivalirudin levels decrease in areas of stagnant blood flow, which may be a problem (especially with VA ECMO). The choice of bivalirudin versus argatroban will often depend on local practice patterns.
- Severe renal failure: Argatroban may be preferred (bivalirudin loses its advantage of a short half-life).
- Severe hepatic failure: Bivalirudin may be substantially preferred (the half-life of argatroban may extend to 2-3 hours, which makes titration and discontinuation a major problem).
dosing & monitoring
monitoring of DTIs:
- DTIs may be monitored based on PTT values.
- Target PTT levels for DTIs are generally the same as PTT targets used with heparin. The target may be personalized based on risk of thrombosis, risk of bleeding, and type of ECMO.
- (Target PTT level in various scenarios is discussed above: ⚡️)
bivalirudin: one dose-titration protocol
- Initial dose:
- GFR < 10: 0.02 mg/kg/hr & discuss with pharmacy.
- CRRT: 0.04 mg/kg/hr.
- GFR 10-29: 0.07 mg/kg/hr.
- GFR 30-60: 0.1 mg/kg/hr.
- GFR >60: 0.15 mg/kg/hr.
- Adjustment based on PTT levels:
- PTT >20 s low: Increase 20%, repeat in 6 hours.
- PTT 10-20 s low: Increase 10%, repeat in 6 hours.
- PTT at target: Repeat in 12 hours.
- PTT 10-20 s high: Decrease 10%, repeat in 6 hours.
- PTT >20 s high: Hold 1 hour, decrease 20%, repeat in 6 hours.
argatroban: one dose-titration protocol
- Initial dose:
- Adjust based on PTT levels:
- PTT >20 seconds low: Increase by 0.2 mcg/kg/min, repeat in 3 hours.
- PTT 11-20 seconds low: Increase by 0.15 mcg/kg/min, repeat in 3 hours.
- PTT 1-10 seconds low: Increase by 0.1 mcg/kg/min, repeat in 3 hours.
- PTT at goal: Repeat in 3 hours, then 6 hours, then q12 hours.
- PTT 1-10 seconds high: Decrease by 0.1 mcg/kg/min, repeat in 3 hours.
- PTT 11-20 seconds high: Hold infusion for 1 hour and decrease by 0.15 mcg/kg/min, repeat in 3 hours.
- PTT >20 seconds high: Hold infusion for 1 hour and decrease by 0.2 mcg/kg/min, repeat in 3 hours. (based on Maybauer 2022)
common causes of DIC in ECMO patients
- Sepsis.
- Thrombosis within the circuit (e.g., membrane lung dysfunction ⚡️)
- Other potential causes of DIC are explored here: 📖
diagnosis of DIC
- The ISTH DIC score may be utilized, as shown below.
- (Further discussion of DIC scoring systems and diagnosis: 📖)
treatment of DIC
- [1] Manage the cause if possible:
- If membrane thrombosis is causative, exchange the membrane or the entire circuit. In the absence of an alternative cause, rising D-dimer predicts the need for circuit exchange. (Maybauer 2022)
- If caused by sepsis, treat the sepsis.
- [2] Supportive management with factor replacement as needed (e.g., for active bleeding).
- (Further discussion of the management of DIC: 📖)
epidemiology
- The incidence might be ~5%, so this is an uncommon but real complication. (Red Book 6e)
diagnosis
- Diagnosis is challenging because both thrombocytopenia and thrombosis are common in the context of ECMO.
- The 4T score appears to have adequate sensitivity (with a score of 0-3 excluding HIT; table below). However, the 4T score may have impaired specificity. (32232501)
- Definitive diagnosis relies upon the detection of platelet-factor-4 antibodies and serotonin release assay (diagnostic algorithm discussed further here: 📖).
treatment for probable/definite HIT
- If there is a significant clinical concern for HIT, anticoagulation should be transitioned to a non-heparin agent while the evaluation is ongoing (either bivalirudin or argatroban).
- Platelet transfusion should be avoided (as this may aggravate thrombosis).
- Heparin-coating of the ECMO circuit doesn't appear to cause or perpetuate thrombocytopenia or thrombosis. (31632747) However, weakly heparin-bonded coating should be avoided if possible. (Red book 6e)
- (Further discussion about the treatment of HIT: 📖).
causes of hemolysis
- Excessive circuit pressures:
- Clot in the circuit:
- Heat exchanger that is malfunctioning.
- Venting Impella (if present).
diagnosis of significant hemolysis
- Plasma free hemoglobin:
- Generally, free hemoglobin is <10 mg/dL. (Maybauer 2022)
- 50-100 mg/dL indicates moderate hemolysis (occurs in ~3% of patients). This should prompt an evaluation of the cause of hemolysis. (Maybauer 2022) In the absence of an alternative explanation, it is concerning for circuit-derived hemolysis. (Schmidt 2022)
- >100 mg/dL indicates severe hemolysis that should prompt immediate action. (Red Book 6e)
- Other causes of elevated plasma-free hemoglobin may include blood transfusion, surgery, and laboratory artifact due to hemolysis within the blood tube.
- Hemolysis index (HI):
- This is an index measured routinely by the chemistry laboratory to evaluate specimens for hemolysis. It is measured by performing spectrophotometry on plasma, so it is fundamentally a measurement of plasma free hemoglobin.
- The hemolysis index correlates linearly with plasma free hemoglobin, with values that might be ~1.5 times higher than the plasma free hemoglobin (figure below).
- Many centers lack immediate access to plasma free hemoglobin measurement, so they may use the hemolysis index instead.
- Urine examination & evaluation:
- Pink urine may occur in severe hemolysis (but this is nonspecific, since it may also occur with minor Foley trauma).
- Urinalysis may be chemically positive for “heme,” without erythrocytes being seen in the sediment.
- Other indices that are less specific:
- LDH >2,000 U/L is suggestive of hemolysis (but LDH correlates poorly with plasma free hemoglobin).
- Falling hemoglobin.
consequences of hemolysis
- Promotes acute kidney injury.
- Promotes thrombus formation by causing platelet activation.
- Free hemoglobin binds nitric oxide, potentially increasing vascular tone.
- Interferes with colorimetric anti-Xa assay. ⚡️
epidemiology
- One series found that plasma free hemoglobin >50 mg/dL was found in 4% of survivors and 16% of nonsurvivors among a mixed population of VV ECMO and VA ECMO. (25902047)
- Hemolysis may be more common in VA ECMO than VV ECMO. (Red Book 6e)
management
- Circuit pressures & tubing chatter must be decreased:
- If clots are present in the circuit and/or membrane:
- Circuit components may need to be changed (e.g., the membrane lung, or the entire circuit).
- Anticoagulation should be optimized to avoid ongoing thrombosis.
- Replace heat exchanger if malfunctioning. (Schmidt 2022)
- Anemia may require PRBC transfusion (discussion of target hemoglobin: ⚡️).
- Hemoglobin >7 g/dL is a adequate for most patients. (38999360)
- Hemoglobin >8 g/dL is a reasonable target with active myocardial ischemia.
- Blood transfusion to target a hemoglobin of 10 g/dL may occasionally be used in efforts to improve oxygen delivery (DO2). However, this should be avoided if possible, given evidence that a restrictive transfusion strategy may improve outcomes. (28704244) Several drawbacks of a higher hemoglobin level should be considered:
- [1] Higher hemoglobin increases blood viscosity – which may impair flow through the circuit and the body.
- [2] Higher hematocrit will increase the tendency of blood to clot.
- [3] Blood transfusion has numerous potential risks (including exacerbation of ARDS, volume overload, infection, immunosuppression, and alloimmunization). Alloimmunization may be especially problematic for patients who require organ transplantation.
- [4] Maintaining a high hemoglobin level is harder than maintaining a lower hemoglobin (e.g., any bleeding causes a greater amount of absolute RBC loss).
- [5] It's unclear whether transfused blood truly improves oxygen delivery to the tissues. (Schmidt 2022)
common sites of bleeding
- Access sites.
- Procedural/surgical site (e.g., post-cardiothoracic surgery).
- Lungs, including hemoptysis related to suctioning (6%).
- Gastrointestinal bleeding (~5%). (36703184)
- Intracranial hemorrhage (~3%).
- Retroperitoneal hemorrhage.
- Hemothorax.
pathophysiology of hemorrhage in ECMO
ECMO patients often accumulate a variety of coagulopathies over time:
- Anticoagulation (e.g., heparin or bivalirudin).
- DIC causing consumptive coagulopathy (e.g., hypofibrinogenemia).
- Thrombocytopenia.
- Platelet dysfunction:
- [1] Uremic platelet dysfunction.
- [2] Medication related (e.g., aspirin, P2Y12 inhibitors).
- [3] Platelet dysfunction caused by loss of glycoproteins Iba and VI receptors on platelets due to exposure to high shear stress in the ECMO circuit. (37519116)
- Acquired von Willebrand syndrome
- Normal functions of von Willebrand factor include:
- (i) Bridge between damaged blood vessels and activated platelets.
- (ii) Carrier for factor VIII (significantly increasing the half-life of factor VIII). (Maybauer 2022)
- High shear forces in ECMO cause depletion of high molecular-weight von Willebrand factor multimers, usually within the first 24 hours. (28898902, Red Book 6e) Levels recover quickly after discontinuation of ECMO. (Red Book 6e)
- Clinical manifestations of acquired von Willebrand syndrome may include diffuse hemorrhage or unexpected bleeding after minor surgery. (Maybauer 2022)
- Diagnosis can be made based on a reduced ratio of vWF activity relative to vWF antigen level. However, in practice, this is difficult to measure and has a long turnaround time.
- Treatment is challenging. Cryoprecipitate can be used to replete vWF as well as VIII levels.
- Normal functions of von Willebrand factor include:
hemorrhage management
evaluation of coagulation status
- Complete blood count.
- Fibrinogen level.
- INR, PTT.
- Anti-Xa level (for patients on heparin).
- TEG.
- Ionized calcium (if undergoing massive transfusion, or dialysis with a citrate anticoagulant).
potential interventions
- Hemorrhage source control. Local hemostatic control is ideal (e.g., packing, surgical control, angiographic embolization).
- PRBC transfusion to replace blood losses.
- Adjust the target level of anticoagulation:
- Temporarily holding anticoagulation may be required for severe hemorrhage (e.g., intracranial hemorrhage).
- For catastrophic bleeding, heparin reversal with protamine may be considered (but this carries a high risk of membrane lung clot formation). 📖 (Maybauer 2022)
- For moderate bleeding, reducing the target level of anticoagulation intensity may be a reasonable compromise.
- Consider increasing the ECMO flow to reduce risk of circuit thrombosis.
- Address other coagulopathies:
- Platelet transfusion for target >50-100 b/L.
- Cryoprecipitate to target fibrinogen levels >150-200 mg/dL.
- FFP may be considered (especially if TEG reveals a prolonged R-time).
- Desmopressin (DDAVP) may be a rational therapy to improve platelet function and alleviate acquired von Willebrand syndrome, but there is no evidence to support its use.
- Calcium administration for hypocalcemia.
- Uncontrollable, life-threatening bleeding has been treated successfully with anti-fibrinolytics (aminocaproic acid or tranexamic acid). However, due to the risk of circuit thrombosis, this should be utilized only for refractory hemorrhage. (Schmidt 2022)
common complications include:
- Pneumonia (including ventilator-associated pneumonia).
- Pulmonary edema and diffuse alveolar hemorrhage (especially with LV dilation in VA ECMO: ⚡️)
- Neuromuscular weakness causing diaphragm dysfunction.
- Pneumothorax.
- Pleural effusion (including hemothorax).
- Pulmonary embolism (discussed further below).
pulmonary embolism (& venous thromboembolic disease)
- Causes of PE:
- [1] Thrombosis at the site of venous cannula.
- [2] Embolization of clots formed within the circuit (VV ECMO).
- Epidemiology: Risk of PE is high (often in the 10-15% range).
- Diagnosis:
- Ultrasonography is the test of choice to evaluate for DVT. A routine DVT study should be performed following decannulation.
- CT angiography may be utilized to evaluate for PE (but this can be challenging due to abnormal contrast flow dynamics).
- Transesophageal echocardiography may identify large, central pulmonary emboli.
- Treatment:
- Anticoagulation is indicated (including potentially an adjustment in anticoagulation intensity).
- For submassive/massive PE, tPA is generally contraindicated in the context of ECMO (based on the underlying complex coagulopathy). Large, central PE may be treated with mechanical thrombectomy. (Further discussion: 📖)
nutritional support
- Nutritional support is generally similar to that of other critically ill patients.
- Orogastric tube access may be preferred to nasogastric tube access, to avoid epistaxis.
- VA ECMO historically was felt to represent a contraindication to enteral nutrition, due to concerns regarding mesenteric ischemia. However, recent evidence has allayed these fears; indeed, there is evidence suggesting that enteral nutrition might actually reduce the risk of mesenteric ischemia. (33609105, 30030574) Following initial resuscitation and stabilization on VA ECMO, enteral nutrition is likely to be safe and beneficial.
- (Further discussion of critical care nutrition is here: 📖)
stress ulcer prophylaxis
- Stress ulcer prophylaxis is generally indicated for patients undergoing ECMO. Patients are critically ill, often mechanically ventilated, and often quite coagulopathic.
- There is no clear evidence regarding the optimal stress ulcer prophylaxis among ECMO patients.
- Proton pump inhibitors (PPIs) may have an advantage of being slightly more effective than H2-blockers (0.5% absolute reduction in clinically significant gastrointestinal hemorrhage based on the PEPTIC trial). (31950977)
epidemiology
- Renal failure requiring dialysis occurs in ~40% of patients on ECMO. This is an enormous problem that increases mortality and may interfere with other therapies (e.g., cardiac transplantation). (Red Book 6e)
causes of AKI include:
- Renal hypoperfusion (and lack of pulsatile blood in VA ECMO).
- Hemolysis.
- Microemboli to the renal vasculature.
- Nephrotoxic medications (list: 📖).
- Congestive nephropathy.
- Inflammatory effects of blood exposure to the circuit and membrane. (Red Book 6e)
- (For a more complete list of the causes of AKI: 📖).
prevention of AKI:
- Minimizing hemolysis:
- Avoid hemolysis by using safe flow rates and pressures.
- Respond rapidly to evidence of hemolysis.
- Avoid insertion of a venting Impella, if possible.
- Avoid nephrotoxins as much as possible (e.g., vancomycin, NSAIDs).
- Target a euvolemic volume status.
investigation of AKI may involve:
- Urinalysis including sediment analysis.
- Measurement of creatinine kinase level.
- Evaluation for hemolysis. ⚡️
- Relevant drug levels (e.g., vancomycin, aminoglycoside, tacrolimus).
- Renal ultrasound.
management
- General supportive care for AKI as discussed here: 📖.
- Hemodialysis may be performed via a separate access site, or via accessing the ECMO circuit. When possible it might be preferable to keep hemodialysis separate from the ECMO circuit, in order to keep the ECMO circuit as simple as possible and to facilitate troubleshooting the ECMO circuit.
hypoxic-ischemic brain injury (aka global brain ischemia)
epidemiology and causes
- Hypoxic-ischemic brain injury is a common complication of ECMO, occurring in 14-61% of patients. (31599814)
- Causes include:
management
- [1] Post-arrest treatment involves standard resuscitative pathways (including targeted temperature management). The ECMO circuit itself may be utilized to control temperature, eliminating the need for other temperature control devices. 📖
- [2] Avoid any long-acting sedatives or opioids that may interfere with neuroprognostication.
ischemic stroke
epidemiology & causes
- Incidence may be ~5-10%.
- Causes include:
- Embolic stroke is most common (especially with VA-ECMO, but paradoxical embolism may occur with VV-ECMO).
- Septic emboli.
- Cerebral sinus vein thrombosis (risk may be increased with jugular vein cannulation).
diagnosis
- CT scan is a cornerstone study:
- CT angiography may help evaluate for large vessel occlusion (LVO).
- CT venography is recommended in VV-ECMO patients to exclude cerebral vein sinus thrombosis. (31599814)
management
- General management strategies for ischemic stroke: 📖
- IV alteplase is contraindicated in ECMO. (31599814)
- Mechanical thrombectomy may be performed for large vessel occlusion.
- Check the circuit for thrombosis and may consider circuit exchange.
- Consider the optimal anticoagulation intensity. This may be very complicated, since anticoagulation in the context of a large stroke can increase the risk of hemorrhagic transformation. For moderate to large stroke, holding anticoagulation for a few days may be considered. (31599814)
cerebral air embolism
- Symptoms may include:
- Alarms indicating air within the ECMO circuit.
- Hemodynamic instability.
- Acute neurologic symptoms (which may include coma, seizure, focal deficits, headache, and/or encephalopathy).
- CT brain should be obtained to evaluate for alternative pathologies. (31599814)
- Treatment is supportive. Maximizing the FiO2 in order to decrease the nitrogen content of the blood may accelerate reabsorption of emboli (treatment is discussed further here: 📖).
ICH (intracranial hemorrhage)
epidemiology
- Risk is ~4%. (33814895)
- Most ICHs seem to be present shortly after ECMO cannulation. (33814895)
- Risk relates largely to anticoagulation and/or consumptive coagulopathies. Specific risk factors include:
- Types of intracranial hemorrhage:
- [1] Intraparenchymal hemorrhage.
- [2] Subarachnoid hemorrhage.
- [3] Subdural hematoma.
investigation
- CT scan with CT angiography +/- CT venography is the test of choice.
management
- Anticoagulation needs to be held and potentially reversed (although reversal may carry high risks of membrane lung thrombosis). ECMO circuit flow may be increased in order to reduce the risk of circuit thrombosis. The duration of holding anticoagulation may depend on patient specifics. Close monitoring for any evidence of thrombosis may help guide management as well (e.g., visual inspection for thrombi, circuit pressures). (33814895)
- Platelets should be maintained at least >50,000. (Red Book 6e)
- Further discussion regarding hematologic investigation and management for bleeding on ECMO is here: ⚡️
- General management strategies for intracranial hemorrhage: 📖
seizures
- Seizures are reported in 1-6% of ECMO patients. (31599814)
- Treatment:
- Propofol and benzodiazepines are likely to be sequestered by the ECMO circuit, so higher doses may be required than usual.
- Levetiracetam doesn't seem to be sequestered substantially (<10% protein binding, LogP -0.6). (31599814)
risk factors for limb ischemia
- Type of ECMO:
- ~1% rate in VV ECMO.
- ~5% rate in VA ECMO.
- Larger bore cannula.
- Peripheral arterial disease.
- Cannulation in the superficial femoral artery.
- Arterial dissection.
- Impaired venous drainage leading to compartment syndrome.
common causes of limb ischemia
- Thrombus formation with distal embolization to the limb.
- Vessel occlusion from the cannula itself. (Red Book 6e)
monitoring & diagnosis of limb perfusion may involve:
- Clinical examination (mottling, temperature, pulses).
- Ultrasound evaluation (spectral Doppler ultrasound may evaluate blood flow, with comparison to the contralateral limb to account for changes in left ventricular ejection). (25296619)
- CT angiography with runoff.
management
- Distal perfusion catheter for VA ECMO (some centers insert routinely, others selectively).
- Wean vasopressors as able.
- Other therapies may include:
- Revascularization strategies (e.g., vascular surgery or interventional radiology).
- Compartment syndrome may require fasciotomy.
- If all else fails, amputation may be needed.
- Rhabdomyolysis may require medical management.
diagnosis of infection is challenging
- ECMO itself triggers a systemic inflammatory response.
- The heater/cooler system prevents fever or hypothermia (common signs of infection).
- CRP or procalcitonin are nonspecific and not usually recommended for patients on ECMO. (Red Book 6e)
- Microbial culture data is often essential (but sorting out infection versus colonization may remain confounding).
common sites of infection
- Pre-existing infection prior to ECMO initiation (e.g., community-acquired pneumonia).
- VAP (ventilator-associated pneumonia).
- Line infection (including cannula sites).
- Surgical site infection.
- Urinary tract infection (although it's often difficult to differentiate infection from colonization; discussed further here: 📖).
pathogenic organisms often reflect nosocomial pathogens
- Most common:
- Gram-positive organisms including MRSA, coagulase-negative staphylococci, and Enterococcus species.
- Gram-negative organisms, including Pseudomonas aeruginosa or Enterobacteriaceae.
- Candida species may be involved, especially among patients repeatedly exposed to broad-spectrum antibiotics.
(Further discussion about the investigation & treatment of infection in the ICU: 📖)
antibiotic pharmacology in ECMO
Below are antibiotics that are more useful for patients on ECMO. Hydrophilic antibiotics have the most predictable pharmacokinetics, although these will have an increased volume of distribution due to the volume of the ECMO circuit. (Interpretation of protein binding, Vd, and LogP are discussed in the section on ECMO pharmacology below: ⚡️)
beta-lactams
- Ampicillin 💉 (25% protein binding; Vd 0.25 L/kg; LogP 1.4). Standard dosage appears to achieve therapeutic targets, but available clinical data is sparse. (37243488)
- Cefazolin 💉 (80% protein binding; Vd 0.2 L/kg; LogP -0.6) Standard dosing is probably adequate, but available data is sparse. (31610538, 35326801)
- Ceftazidime 💉 (15% protein binding; Vd 0.3 L/kg; LogP -1.6). Pharmacokinetics unaffected by ECMO. (35326801)
- Ceftriaxone 💉 (90% protein binding; Vd 0.2 L/kg; LogP -1.7). Standard dosing appears to achieve therapeutic targets. (35253107; 29732181)
- Cefepime 💉 (20% protein binding, Vd 0.3 L/kg; LogP -0.1). Unlikely to be affected by ECMO.
- Ceftaroline 💉 (20% protein binding; Vd 0.3 L/kg; LogP -3.7). Unlikely to be affected by ECMO.
- Piperacillin-tazobactam 💉 (30% protein binding; Vd 0.3 L/kg; LogP 0.5). Dosing may be similar to other critically ill patients. (29732181, 34460303, 33569597)
- Meropenem 💉 (2% protein binding; Vd 0.35 L/kg; LogP -0.7). Dosing similar to other critically ill patients, with several studies showing no change in pharmacokinetics due to ECMO. (29732181, 35326801, 34460303)
other antibiotics
- Doxycycline 💉 (80% protein binding; Vd 0.75 L/kg; LogP 0.6). Data is extremely limited, but one case report found adequate pharmacokinetics. (Mehta et al.)
- Linezolid 💉 (30% protein binding; Vd 0.6 L/kg; LogP 0.9). Despite hydrophilicity, some case reports describe inadequate levels when using linezolid. (32426841, 35326801, 33239110, 23453617) Ceftaroline might be preferable for therapy of MRSA pneumonia.
- Metronidazole 💉 (20% protein binding; Vd 0.7 L/kg; LogP -0.18). Unlikely to be affected by ECMO.
- Fluoroquinolones: 💉
nephrotoxic antibiotics with potential therapeutic dose monitoring
- Vancomycin 💉 (50% protein binding; Vd 0.7 L/kg; LogP -3.1). Dosing similar to other critically ill patients (e.g., loading dose of 25-30 mg/kg followed by 30-40 mg/kg/day). (35326801) Careful monitoring of levels is required. (29732181) Vancomycin use should be avoided if possible, to reduce the risk of renal failure.
- Aminoglycosides 💉 (<30% protein binding; LogP <0). Volume of distribution is often increased, but aminoglycosides aren't adsorbed by the circuit. Close monitoring should be utilized. The primary drawback is nephrotoxicity and limited penetration of certain tissues.
antifungal therapies
- Fluconazole 💉 (10% protein binding; Vd 0.7 L/kg; LogP 0.4). Minimal sequestration seems to occur with the ECMO circuit. (35326801)
- Voriconazole 💉 (60% protein binding; LogP 1). Significant drug adsorption to circuit seems to occur (71% circuit drug loss in one report). (29732181)
- Caspofungin 💉 (95% protein binding; ; Vd 0.3-2 L/kg; LogP -3.8). Usual doses are likely adequate, although studies are conflicting. (32816724, 37300631)
- Micafungin 💉 (>99% protein binding; Vd 0.2 L/kg; LogP 0.4). Studies are limited, with some suggesting no difference, but the EMPIRICUS study suggests a 23% reduction in area under the curve. (37300631) A dose escalation to ~150 mg/day is likely adequate.
general approach for determining risk of ECMO circuit sequestration
- Protein binding <30% (low):
- LogP <1 & Vd <1 L/kg: Low risk.
- LogP 1-2 & Vd 1-5 L/kg: Low to moderate risk.
- LogP >2 & Vd >5 L/kg: Moderate risk (consider increasing dose/frequency).
- Protein binding 30-60% (moderate):
- LogP <1 & Vd <1 L/kg: Low-to-moderate risk.
- LogP 1-2 & Vd 1-5 L/kg: Moderate risk (consider increasing dose/frequency).
- LogP >2 & Vd >5 L/kg: Moderate-to-high risk (use higher loading and/or maintenance doses and/or increase frequency)
- Protein binding >60% (high):
- LogP <1 & Vd <1 L/kg: Moderate risk (consider increasing dose/frequency).
- LogP 1-2 & Vd 1-5 L/kg: Moderate-to-high risk (use higher loading and/or maintenance doses and/or increase frequency)
- LogP >1 & Vd >5 L/kg: High risk (avoid if possible; if required use higher loading doses and/or maintenance doses and increased frequency if appropriate; follow medication levels if available). (Red Book 6e)
- (Log P is the octanol-water partition coefficient. High Log P values indicate greater lipophilicity.)
- ⚠️ When possible, pharmacokinetic data should be sought regarding individual medications. The above approach is a general guide to utilization that is particularly useful for medications whose ECMO pharmacology hasn't been well investigated.
general strategies for optimizing pharmacokinetics
- Select a more hydrophilic drug, if possible.
- IF possible, select medications with wider therapeutic index (which are more forgiving pharmacokinetically).
- Titrate drugs to level or effect:
- [1] If drug level can be checked (e.g., vancomycin, phenobarbital), follow this carefully.
- [2] For sedatives/analgesics, administration in boluses PRN may allow dose personalization while avoiding drug accumulation (which may result from infusions that aren't continuously and aggressively weaned down).
major pharmacologic issues in ECMO
- [1] Increased volume of distribution (especially affects hydrophilic medications with a low Vd):
- Additional volume of blood in circuit.
- Fluid given to promote adequate circuit preload.
- [2] Sequestration (especially affects highly lipophilic and protein-bound drugs):
- Drugs adhere to the plastic of circuit.
- Initially, sequestration may decrease drug levels.
- Later on, reabsorption of drugs from the circuit may lead to toxicity.
- Sequestration may be greatest with newly primed circuits. (Red Book 6e)
- [3] Protein losses (affects highly protein-bound drugs):
- Albumin levels may decrease, due to adsorption of protein onto the circuit.
- Lower albumin levels may increase free drug levels.
antibiotic pharmacology: ⚡️
analgesia & sedation
Most neuroactive medications are lipophilic (since this is required to penetrate the brain). This causes many sedatives and analgesics to have relatively high adsorption to the ECMO circuit. However, since many of these drugs are titrated to effect, they may still be used effectively – albeit with higher doses and closer attention to dose titration.
nonpharmacologic therapies to improve comfort
- Adequate CO2 clearance: For patients with tachypnea or ventilator dyssynchrony, increasing the sweep speed may reduce the pCO2 and thereby blunt the respiratory drive. (More on sweep gas titration: ⚡️)
- Treat hypernatremia, since this may promote thirst and agitation. 📖
acetaminophen 💉
- Acetaminophen has favorable pharmacokinetics in ECMO (20% protein binding; LogP 0.5).
- Scheduled acetaminophen may provide a mild amount of analgesia with minimal toxicity. Efficacy is low and gradual-onset, so it's generally optimal to provide this on a scheduled basis (rather than PRN).
opioids
- Pharmacokinetics:
- 🏆 Hydromorphone: 10% protein binding; LogP 1.5
- Fentanyl: 80-85% protein binding; LogP 4.1
- Morphine: 30-40% protein binding; LogP 0.9
- Hydromorphone has low lipophilicity and protein binding, so it may be a good choice for routine PRN analgesia. Some studies suggest that use of hydromorphone correlates with reduced opioid requirements and improved days alive without delirium or coma, as compared to fentanyl. (38999360)
- Fentanyl may be useful for very brief analgesia (e.g., for procedures).
propofol
- Pharmacokinetics: 95-99% protein binding; LogP 3.8.
- Propofol is safe to use with current membrane oxygenators. However, it will be substantially sequestered within the ECMO circuit, so higher doses may be required. Unfortunately, it's unclear how the need for higher propofol doses may be balanced with minimization of propofol infusion syndrome.
central alpha-2 agonists
- Dexmedetomidine infusion: 💉
- Pharmacokinetics: 94-97% protein binding; LogP 2.8
- Dexmedetomidine is highly lipophilic and protein-bound, so it will be substantially adsorbed by the circuit. Higher doses of dexmedetomidine may be required, especially if there is a circuit change. (Red Book 6e)
- Enteral guanfacine: 💉
- Pharmacokinetics: 70% protein binding; LogP ~1.7 (PubChem).
- Guanfacine is likely to be sequestered in the ECMO circuit, but high doses could be trialed.
ketamine
- Pharmacokinetics: ~35% protein binding; Log P ~3.
- Ketamine may be adsorbed by the circuit, leading to lower levels. However, numerous studies describe the successful use of ketamine among patients on ECMO.
phenobarbital
- Pharmacokinetics: 50% protein binding; LogP 1.5
- Extremely slow metabolism and the ability to check phenobarbital levels facilitate safe titration of phenobarbital to effect.
- Phenobarbital may be a useful agent for adjunctive sedation in the context of ECMO. (Curran et al.)
benzodiazepines
- Pharmacokinetics:
- Midazolam: 97% protein binding; LogP 3.9
- Lorazepam: 85% protein binding; LogP 2.2
- Diazepam: 98% protein binding; LogP 2.8
- Benzodiazepines will have a reduced duration of effect, due to clearance by the ECMO circuit.
- Midazolam could be useful for procedural sedation.
- Benzodiazepines are not generally preferred agents in the ICU due to increased risk of ICU delirium.
antipsychotics
- Pharmacokinetics:
- Haloperidol: 90% protein binding; LogP 4.3
- Quetiapine: 80% protein binding; LogP 2.8
- Olanzapine: 93% protein binding; LogP 4
- Lurasidone: 99% protein binding; LogP 5.6
- Chlorpromazine: >90% protein binding; LogP 5.4
- Overall, antipsychotics are likely to be substantially sequestered by the ECMO circuit. IV haloperidol could be utilized for behavioral emergency. However, ongoing use of adjunctive atypical antipsychotics seems unlikely to achieve pharmacokinetic targets. There is also a risk that once the circuit is saturated with drug, levels could accumulate leading to oversedation.
valproic acid 💉
- Pharmacokinetics: 90-95% protein binding; LogP 2.8
- Valproic acid has mood-stabilizing properties that may be useful for the management of some patients with persistent agitated delirium that is refractory to more commonly utilized agents.
- Valproic acid has been used successfully in ECMO patients for seizure management. (33198577) It could be considered for refractory agitation. An advantage of valproic acid is the ability to measure drug levels (however, some caution is required when measuring total valproate level, since the free level may be proportionally higher among patients with hypoalbuminemia).
There are innumerable possible ECMO configurations. The following discussion refers to the most common ones.
VV ECMO with two cannulas
The distance between the two cannulas should ideally be >10-15 cm to avoid recirculation. (33272724)
femorojugular configuration
- Venous drainage cannula: Distal tip is below the IVC/RA junction, near the hepatic vein.
- Arterial return cannula: Distal tip at the SVC/RA junction.
(femorofemoral configuration; less common)
- Venous drainage cannula: Distal tip in the lower IVC, 5-10 cm below the RA/IVC junction, above the bifurcation of the iliac veins. (33272724)
- Arterial return cannula: Distal tip in the right atrium.
VV ECMO with a single catheter
Avalon catheter (bicaval dual lumen catheter)
- Return port is within the RA pointed towards the tricuspid valve. If the arterial outflow is pointing away from the tricuspid valve, this may promote recirculation.
ProtekDuo catheter (veno-pulmonary artery ECMO)
- This is a single, dual-lumen cannula positioned similarly to a Swan-Ganz catheter with the tip of the catheter sitting in the main pulmonary artery.
- Drainage ports should project over the right atrium. (33272724)
peripheral VA ECMO
- Venous drainage cannula:
- Often at the junction of IVC and right atrium (a few cm above the diaphragm).
- Sometimes it may be inserted through the right atrium, with the distal tip at the SVC/RA junction. (Shepard 2019)
- Arterial return cannula:
- Usually in the common iliac artery or distal aorta.
- (Doesn't require daily radiograph.)
indications
- Indications are similar to non-pregnant populations.
- The fetus is an end-organ, so fetal distress may indicate inadequate systemic perfusion or gas exchange.
- More common indications include:
- ARDS.
- Pulmonary embolism.
- Amniotic fluid embolism.
- Pulmonary hypertensive crisis.
- Peripartum cardiomyopathy.
gas exchange targets
- Oxygenation target is often a PaO2 ≧70 mm and oxygen saturation ≧95% to ensure fetal oxygenation.
- PaCO2 is normally ~27-32 mm in pregnancy, so a mild respiratory alkalosis should usually be targeted.
- (Further discussion of normal blood gas parameters in pregnancy: 📖).
medications
- Anticoagulation: Either heparin or DTIs may be used (similarly to other ECMO patients). (Red Book 6e)
- Steroid: dexamethasone or betamethasone have higher fetal uptake (discussed further: 📖)
patient selection for VV ECMO
VV ECMO is a bridge to:
- Recovery of native lungs (most patients).
- Lung transplant (for a patient with irreversible lung disease who is a lung transplant candidate). (33965970)
contraindications to VV ECMO
- Central nervous system hemorrhage.
- Significant central nervous system injury.
- Irreversible and incapacitating central nervous system pathology.
- Systemic bleeding.
- Contraindication to anticoagulation (e.g., severe coagulopathy).
- Immunosuppression.
- Older age (increasing risk of death with increasing age; no threshold is established).
- Mechanical ventilation for more than 7 days with Pplat >30 cm and FiO2 >90%. (33965970)
general indications for VV ECMO
- Hypoxemic respiratory failure (P/F <80 mm) after optimal medical management including a trial of prone positioning (if possible).
- EOLIA trial criteria: P/F <50 for >3 hours, or P/F <80 for >6 hours despite optimization including measures such as paralysis, proning, and inhaled pulmonary vasodilators. (38999360)
- Hypercapnic respiratory failure (pH <7.25 with PaCO2 >60 mm) despite optimal conventional mechanical ventilation (respiratory rate 35 b/m and plateau pressure ≦30 cm).
- Lung transplantation: Support as a bridge to lung transplantation or primary graft dysfunction following lung transplantation. (33965970)
common situations where VV ECMO may be beneficial
- ARDS.
- Acute eosinophilic pneumonia.
- Pulmonary hemorrhage (including diffuse alveolar hemorrhage). Anticoagulation may be omitted or utilized at a reduced intensity, while accepting an increased risk of device-related complications. (Red Book 6e)
- Severe asthma.
- Thoracic trauma (e.g., traumatic lung injury and severe pulmonary contusion).
- Severe inhalational injury.
- Massive air leak syndromes (e.g., large bronchopleural fistula). (38999360)
- Peri-lung transplant (e.g., primary lung graft dysfunction and bridge to transplant). (33965970)
patient selection for VA ECMO
VA ECMO is a bridge to:
- [1] Recovery of native heart, e.g.:
- Time to recover (e.g., viral myocarditis).
- Bridge to procedure (e.g., revascularization, pulmonary embolectomy).
- [2] Durable LVAD.
- [3] Heart or heart-lung transplantation.
contraindications to VA ECMO
- Cardiac recovery unlikely and not a candidate for heart transplant or durable LVAD.
- Poor life expectancy (e.g., end-stage peripheral organ diseases, advanced malignancy, chemotherapy-induced chronic cardiomyopathy).
- Severe vascular disease (including axillary arteries).
- Acute Type A or B aortic dissection with extensive aortic branches involved.
- Severe aortic regurgitation.
- Severe neurological impairment (e.g., prolonged anoxic brain injury, extensive trauma, or hemorrhage).
- Severe immunosuppression.
- Contraindication to anticoagulation (e.g., severe coagulopathy).
- Cirrhosis (Child-Pugh class B and C; online calculator here 🧮).
- Older age (higher risk of mortality; no threshold is established). (34339398, Red Book 6e)
common situations where VA ECMO may be beneficial
- Fulminant myocarditis.
- Acute MI.
- Intoxication with cardiotoxic drugs.
- Hypothermia with refractory cardiocirculatory instability.
- Massive pulmonary embolism.
considerations
- VA ECMO should be considered for cardiogenic shock within 6 hours of its occurrence, refractory to conventional pharmacology and fluid therapy, in patients with reversible cardiocirculatory collapse or those eligible for LVADs or transplant. (34339398)
- Prognostic scores may be used to provide information regarding decision making before ECMO.
- SAVE score predicts survival after VA ECMO (MDCalc: 🧮).
To keep this page small and fast, questions & discussion about this post can be found on another page here.
Acknowledgement: Thanks to Dr. Scott Weingart (@emcrit) for thoughtful comments on this chapter.
References
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Books
- MacLaren, G. (2022). Extracorporeal Life support: The ELSO Red Book 6th Edition.
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