ECMO manual

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 be ~5 L/min initially.
- ⚠️ Increasing pump flow may increase the recirculation fraction. Thus, further increases in pump flow may not substantially improve oxygenation beyond a certain point.

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.
- Avoid left ventricular dilation. ⚡️

V̇ (ECMO blood flow)

ECMO flow & general maximization of safety

Low flow (<2-3 L/min) may increase thrombosis risk:
- If anticoagulation isn't safe, then high flows (e.g., 4-5 L/min) should minimize clot formation within the circuit. (31632747)
  - One expert consensus statement recommended keeping flow >3.5 L/min if not on anticoagulation in VA or VV ECMO. (34559091)
  - The Red Book (6e) states that anticoagulation can be held for prolonged periods in VV-ECMO if necessary, with a flow rate maintained at >2.5-3 L/min. (Red Book 6e)
High flows will increase a variety of hematologic side effects:
- Hemolysis.
- Shear-induced platelet surface receptor shedding.
- Loss of von Willebrand multimers. (34559091)

ECMO blood flow in VV ECMO

In native lung failure, an ECMO flow >~60% of the estimated cardiac output is generally adequate. (38999360, 40047223) This depends on several factors, including:
- [i] If the native lung is providing some oxygenation, then less flow will be required.
- [ii] If S_vO₂ is higher, then less flow is required.
Initially, flow is usually ~5 L/min (max ~7-8 L/min).
Safest range? ~3-6 L/min is generally safe (although this may vary depending on equipment and patient factors). (Red Book 6e)
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).

intravascular pressures
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hemodynamic monitoring on VV ECMO

VV ECMO is more similar to monitoring usual ICU patients.

key differences include

Swan-Ganz thermodilution overestimates cardiac output.
CVP may be used to evaluate access insufficiency, but it doesn't necessarily function as a marker of RV preload.
Tricuspid regurgitant velocity can't be used to estimate pulmonary artery pressure. (30865613)

hemodynamic monitoring in VA ECMO

evaluation of native cardiac output (CO_native)

Pulse pressure <15 mm suggests CO_native <1 L/min. (40167014)
- (Discussed further in the section below on LV distension.)
etCO2 <15 mm suggests CO_native <1 L/min. (40167014)
- (Discussed further above in the section on etCO2 📖).
Echocardiographic VTI may be the best indicator. (40167014)
(Swan-Ganz thermodilution doesn't work.)

indicators of perfusion

Skin perfusion:
- Capillary refill time.
- Central-to-peripheral temperature gradient.
- (Perfusion index doesn't work, due to nonpulsatile perfusion.)
Urine output.
S_vO₂ ⚡️ (if not confounded by differential oxygenation).
NIRS ⚡️
Lactate (only if no other sources of elevated lactate, such as an epinephrine infusion).

indicators of preload

LV preload:
- Cardiogenic pulmonary edema, or a B-line pattern on lung POCUS, implies elevated wedge pressure.
- LV end-diastolic volume (LVEDV) reflects LV preload and can be evaluated directly with POCUS.
- Pulmonary capillary wedge pressure is the gold standard.
ECMO preload:
- P_ven may trend with preload at a fixed pump RPM. However, there are numerous other causes of low P_ven aside from decreased preload (discussed below ⚡️).

indicators of preload responsiveness

Native cardiac preload dependence:
- Passive leg raise test, or the Trendelenberg maneuver (>12% increase in etCO2 suggests fluid responsiveness with reasonable performance). (41261273)
ECMO-pump is preload dependent:
- Passive leg raise test or Trendelenberg maneuver.
- Mini-fluid challenge.
- (Evaluate effectiveness by simply looking at the ECMO flow.)

P_ven (venous pressure) & drainage insufficiency

This is the pressure before blood enters the pump. It reflects the 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 P_ven (aka drainage insufficiency)

[1] Inadequate preload:
- Hypovolemia, e.g.:
  - Hemorrhage.
  - Vasodilation.
- Excessive intrathoracic pressure:
  - Pneumothorax.
  - Excess PEEP.
  - Coughing or bucking the ventilator (treatment may include optimization of ventilatory synchrony, increasing sweep flow to reduce respiratory drive, and opioids to suppress respiratory drive).
- Excessive intra-abdominal pressure:
  - Abdominal compartment syndrome.
  - Patient is bearing down.
- Tamponade ⚡️ may compress the right atrium and impede venous drainage.
- Native cardiac recovery (VA ECMO only; the heart and ECMO circuit compete for preload).
[2] Venous cannula or tubing problem:
- The venous catheter is kinked.
- The catheter is malpositioned (especially in the hepatic vein). (30865613)
- Venous catheter clot (inspect the circuit for clots).
- The cannula is too small (consider the addition of a second drainage cannula).
[3] Excessive pump speed.

management of drainage insufficiency

[1] Confirm pre-pump chugging:
- Flow drops (1-2 liters below baseline).
- Pven < -100 mm.
- Distinguish from post-pump chugging (which may result from high MAP, arterial cannula kinking, or oxygenator thrombosis). (40106084)
[2] Gradual reduction of pump speed:
- Decrease by ~100 RPM every 10 seconds until a stable flow is achieved.
- 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)
- Is it possible to sufficiently support the patient with a lower pump speed? (If support is inadequate, careful up-titration of the pump speed may be required.)
[3] If recurrent drainage insufficiency occurs: Evaluate & treat for:
- ECMO circuit:
  - ? Venous line kinking.
  - ? Drainage cannula malposition.
  - ? Drainage cannula clot.
- Patient assessment:
  - ? Evidence of bleeding.
  - ? Vasodilation.
  - ? Agitation or coughing.
  - ? Tension pneumothorax.
  - ? Tamponade. ⚡️
  - ? Abdominal hypertension. (32295631, 40106084)
- Tests to consider may include:
  - CBC if concerned for bleeding.
  - Chest radiograph (evaluate for tension pneumothorax, cannula malposition).
  - POCUS (evaluate for pneumothorax; tamponade; cannula malposition in hepatic vein).
[4] For persistent drainage insufficiency:
- Assess fluid responsiveness (e.g., trial of Trendelenburg position).
- If the patient appears fluid responsive, volume resuscitation is indicated. (32295631)
[5] For persistent drainage insufficiency:
- Last resort: placement of an additional drainage catheter.

P_Int (internal pressure)

This is the highest pressure in the ECMO circuit.
It reflects the pressure required to push blood through the membrane and tubing and back into the body.
The goal value is <300 mm to avoid hemolysis (although hemolysis may occur at pressures >250 mm).

▵P (transmembrane pressure)

This is discussed in the section below on membrane lung dysfunction. ⚡️

P_Art (arterial pressure)

This reflects the pressure required to push blood through the arterial return cannula and into the body.
Very high P_Art (e.g., >300 mm) can cause hemolysis.

return obstruction (high P_Art, high P_Int, stable △P)

High return cannula resistance:
- The return cannula is kinked or externally compressed.
- The return cannula is incorrectly positioned (including aortic dissection in the case of VA ECMO).
- The return cannula is clotted.
- The return cannula 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 obstruction

Check the circuit for any kinks or external pressure on the cannula.
Evaluate for problems listed above.
Vascular imaging may be needed.

**MAP (only for VA ECMO)**

MAP goal in VA ECMO

Most authors suggest targeting a MAP of 65-80 mm. (31219839, 32197690, 34559091)
Lower MAPs (60-65 mm):
- 🙁 Risk of hypoperfusion.
- 🤷‍♂️ May be adequate in patients with intact perfusion, especially patients with chronic hypotension. Pay close attention to perfusion indicators (discussed above ⚡️).
Higher MAPs:
- 🙁 May increase LV afterload, causing LV dilation and cardiogenic pulmonary edema.
- 🙁 May increase the risk of intracranial hemorrhage (if very high).
- 🤷‍♂️ May be tolerated for patients with isolated RV dysfunction. Higher MAP may also be required under certain situations, such as intra-abdominal hypertension or pressure-dependent arterial stenosis. (34559091)

hypotension in VA ECMO

MAP = [Native cardiac output + V̇](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 the ejection fraction is reduced, 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).

hypertension in VA ECMO

Assess volume status; diurese if indicated.
Assess SVR; if high, then reduce vasopressor.
If improved ventricular function is seen on echocardiography:
- Reduce inotrope dose.
- Consider a reduction in ECMO flow.

oxygenation
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S_vO₂ (venous drainage oxygen saturation)

general S_vO₂ interpretation

Low S_vO₂ is generally bad (e.g., <60% in VV ECMO or <65% in VA ECMO):
- VV ECMO: Targeting a S_vO₂ >60% is a convenient index of adequate oxygenation. (Red Book 6e)
- VA ECMO: S_vO₂ should ideally be >65-70%. (Red book 6e; 65% Choi 2019 31364329)
- Causes & management of low S_vO₂ are discussed further below.
OK values: ~60-80%. (40167014)
High SvO2 isn't necessarily good:
- VV ECMO:
  - Recirculation ⚡️ may cause rising S_vO₂ with falling systemic oxygen saturation (SaO2).
  - S_vO₂ >75% suggests recirculation. (Maybauer 2022)
  - S_vO₂ >80% strongly suggests recirculation. (34559091)
- VA ECMO: If the venous and arterial catheters are below the heart, a high SvO2 in the lower extremity may reflect differential hypoxemia (north-south syndrome) ⚡️. Blood in the lower part of the body isn't mixing with blood in the upper part, so blood in the lower body becomes hyperoxygenated.
- High S_vO₂may also reflect hyperdynamic shock states (e.g., septic shock).

causes of low S_vO₂

Systemic hypoxemia.
Shock.
Anemia.
Increased oxygen consumption (e.g., fever, shivering).

management of low S_vO₂ may include

Management of systemic hypoxemia (if present).
- Systemic desaturation in VV ECMO: ⚡️
- Systemic desaturation in VA ECMO: ⚡️
Increase systemic blood flow:
- VV ECMO: If cardiogenic shock has developed, treat it (e.g., by adding 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).
- Forced normothermia or even mild hypothermia may be considered (e.g., 36 °C for normothermia). This may be achieved by altering the ECMO blood rewarmer. (33965970)
PRBC transfusion may be considered (although efficacy is unclear; discussed further here: ⚡️).

F_dO₂ (fraction of delivered O2), aka FsO2 (fraction of sweep gas O2)

VV ECMO

F_dO₂ is generally set to 100%.
- This hyperoxygenates the blood, but this blood mixes with venous blood before reaching tissues.
F_dO₂ is decreased during weaning from VV ECMO.

VA ECMO

Unlike VV ECMO, blood is delivered directly to the tissues. This creates a risk of tissue hyperoxia.
Adjust F_dO₂to target slight hyperoxemia (PaO2 ~150 mm) after the oxygenator. (34339398)

S_arO₂ (arterial return saturation) & P_arO₂ (pO2 in arterial return)

VV ECMO

S_arO₂ should be ~100%.
P_arO₂ should be >600 mm with a new gas-exchange device. P_arO2 will decrease over time, but should remain above ~250 mm (<150-200 mm is abnormally low; see possible causes listed below). (Schmidt 2022)

VA ECMO

S_arO2 should be close to 100%.
The target P_arO2 is adequate for oxygen delivery, but not markedly hyperoxic (see the section above regarding F_dO₂).
P_arO2 should be >2-5 times the F_dO₂ (e.g., if the F_dO₂ is 30%, then the P_arO₂ should be >60-150 mm). (Red Book 6e)

causes of low SarO2 & low ParO2

[1] F_dO₂ is set too low (see the section above on F_dO₂).
[2] If the blood flow rate is exceptionally high (near the membrane lung's rated flow) and the S_vO₂is <60%, then low S_arO2 and P_arO2 are inevitable. (Red Book 6e)
[3] Membrane lung dysfunction. ⚡️
- In general, a P_arO₂ <200 mm (with FdO2 of 100%) should prompt consideration of replacing the membrane. (34559091)

mechanical ventilator settings regarding oxygenation

VV ECMO or central VA ECMO: total lung rest settings

With these configurations, the membrane lung supplies blood to the entire body. The patient's lungs can be rested completely, and the membrane lung can do all of the work.
PEEP: ≧10 cm is recommended (10-24 cm is an acceptable range). (33965970)
- Insufficient PEEP may lead to atelectasis. (33965970)
- Excessive PEEP could:
  - Impair venous return (into the drainage cannulae, leading to low P_ven).
  - Impair RV function.
  - Produce an excessively high plateau pressure. (33965970)
Plateau pressure: the recommended target is <25 cm (≦ 30 cm is acceptable). (33965970)
Driving pressure ≦10 cm. (Bagchi 2025)
Tidal volume ~4 cc/kg ideal body weight.
Respiratory rate of 5-10 breaths/minute. (4-15 per ELSO 33965970)
- CO2 clearance can be easily achieved with sweep flow, so minute ventilation should be minimized to reduce mechanical power delivery to the lungs.
- Reducing the respiratory rate will cause a linear reduction in mechanical power delivered to the lungs. (34597688)
FiO2:
- An optimal FiO2 range might be 30-50%. (33965970)
- FiO2 should be low enough to avoid oxygen toxicity. The level of FiO2 at which oxygen toxicity occurs is unclear but may be as low as ~60-70%. (23271823)
- FiO2 should be high enough to assist with systemic oxygenation (this may reduce the required ECMO circuit flow).
Example on PCV (pressure control ventilation):
- Respiratory rate 10.
- PEEP 10 cm.
- Inspiratory pressure 10 cm initially (but down-titrate to target 2-4 cc/kg tidal volume).
- FiO2 50% (range 30-50%).
Example on volume cycled ventilation:
- Respiratory rate 10.
- Tidal volume 4 cc/kg (target plateau ≦24 cm), PEEP ≧10 cm.
- FiO2 50% (range 30-50%).
Example on APRV:
- P-Hi 15 cm.
- T-hi 6 seconds (or higher – increasing T-hi reduces mechanical power administration to the lung while improving recruitment).
- T-low 0.3 seconds.
- FiO2 30-50%.

VV ECMO or central VA ECMO: partial lung rest settings with some oxygenation

If there is difficulty obtaining adequate systemic oxygenation, the lungs may be gently recruited (e.g., using a slightly higher PEEP or P-Hi than described above) and the FiO2 may be liberalized somewhat (e.g., to 60-65% FiO2).
The respiratory rate is kept extremely low, so the mechanical power delivered to the lungs remains minimal.
This minimizes iatrogenic lung injury while simultaneously reducing the required circuit flow rate (thereby avoiding hemolysis).

peripheral VA ECMO (with ejection): native lung oxygenation must always be adequate

With peripheral VA ECMO, the native lungs are providing oxygenation to the heart and brain.
Adjust PEEP and FiO2 to achieve an adequate PaO₂ & oxygen saturation in the right arm.
- PaO2 in the right arm should be <120 mm to reduce the risk of cerebral hyperoxia. (Red Book 6e)
- Cerebral NIRS may also be used to assess adequate oxygenation (discussed below).
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)
(To provide lung protection, the respiratory rate can often be kept low while leaning on the ECMO circuit to clear most of the CO2. This is discussed above, in the section on CO2 clearance in VA-ECMO.)

S_pO₂(patient's oxygenation)

S_pO₂ goal on VV ECMO

Goal 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, 32197690, 34559091)
PaO2 target is often >45-50 mm. (30865613)

S_pO₂ goal on VA ECMO

Goal of >~90%. (34559091)

S_pO₂ goal in pregnancy

Oxygenation: PaO2 ≧70 mm and an oxygen saturation ≧95% to ensure fetal oxygenation.

NIRS to evaluate CNS perfusion

rSO2 >50% might be a therapeutic target. (40167014)
rSO2 <40% indicates cerebral desaturation & risk of brain injury.
rSO2 asymmetry >8% is worrisome.
- May indicate a regional stroke.
- May indicate VA-ECMO with differential hypoxemia.
If rSO2 is lower in the brain than in the leg, this suggests differential hypoxemia. ⚡️ (34559091)
⚠️ Paradoxically, in VA-ECMO, rising rSO2 may sometimes indicate native cardiac failure which is causing the mixing point to move proximal to the bracheocephalic arteries. (30865613)

NIRS to evaluate limb perfusion

A sustained rSO2 <50% indicates inadequate limb perfusion.
A rSO2 differential >15% between legs also supports regional hypoperfusion. (29848162)

CO2 clearance
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sweep gas flow rate

sweep 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).

sweep flow in VV ECMO or central VA ECMO

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 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 is causing harm, such as right ventricular failure). (Red Book 6e; Maybauer 2022)
- Correct pCO2 by no more than 50% over the first 4 hours. (Bagchi 2025)
⚠️ When sweep flow is adjusted, it may take as long as 50 minutes for the arterial pCO2 to equilibrate. (34559091)

subsequent titration of sweep flow

[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.
- Even in patients on VA ECMO with differential ventilation, increasing the sweep speed still reduces respiratory drive and patient comfort.
[2] PaCO2 (e.g., targeting a safe pH). The sweep flow rate is inversely proportional to the PaCO2 level, as indicated by the following equation: (Red book 6e)
- (New sweep) = (Current sweep)(Current CO₂/Desired CO₂)
⚠️ For patients on ultra-lung-rest settings, a low pCO2 may facilitate patient comfort and reduce the work of breathing (as discussed above). Thus, if a patient is comfortable with a mildly low pCO2 (e.g., 30 mm), this may be fine. (Schmidt 2022) However, a normal pCO2 may be desirable to promote adequate brain perfusion in the presence of elevated intracranial pressure.

weaning off VV ECMO

As the lungs recover, PaCO2 may start to decrease, allowing sweep flow to be reduced.
If the sweep is <1 L/min, native lungs are eliminating nearly all of the CO2.

sweep flow in peripheral VA ECMO

In peripheral VA ECMO, patients should ideally have differential gas exchange:
- The ECMO circuit primarily clears CO2 from the lower body.
- The patient's lungs primarily ventilate the upper body.
Getting started:
- Immediately after VA ECMO initiation, avoid any rapid falls in pCO2 (as discussed above for VV-ECMO).
- If you're targeting a normal pCO2 level, matching the sweep gas flow to the blood flow in a 1:1 ratio is often a helpful starting point for ongoing titration. (39869669)
For most patients, sweep flow should be titrated against the P_arCO₂ (CO2 level in blood leaving the ECMO circuit).
⚠️ Beware of titrating sweep flow against the right radial artery pCO2 in patients whose lungs are functioning well. If the lungs are efficiently clearing CO2 and the patient is hyperventilating, the radial pCO2 may be substantially below the P_arCO₂. (39869669) However, in selected situations (e.g., for patients with severe lung injury), it may be reasonable to titrate the sweep flow based on the right radial artery pCO2 (discussed further in the section below on Membrane-Predominant CO2 Clearance).

mechanical ventilator settings regarding CO₂ clearance

VV ECMO, or central VA ECMO

In these configurations, blood from the membrane lung perfuses the body.
To rest the lung, it's often helpful to reduce the ventilator rate and use the sweep gas flow to clear CO2.

peripheral VA ECMO: conventional ventilation strategy

Titrate minute ventilation against the P_aCO₂ in the right wrist.
- Try to match perfusion with ventilation (e.g., if only 2 L/min of blood flows through the lungs, minute ventilation should be reduced accordingly to avoid overventilation).
Titrate sweep speed against the P_arCO₂ (ECMO return blood). (39557688)

peripheral VA ECMO: MPCC strategy (Membrane-Predominant CO2 Clearance)

Reduced CO2 clearance by the native lungs may be mandatory and/or desirable in the following situations:
- [1] Native lung ventilatory failure develops, making it impossible to achieve normal CO2 clearance without using lung-injurious mechanical ventilation.
- [2] In the context of acute lung injury, it may be desirable to minimize mechanical power being delivered to the lung (thereby promoting lung-protective ventilation).
Partial lung rest can be achieved by increasing sweep speed and reducing the minute ventilation (so that CO2 is cleared predominantly via the membrane lung): (Red Book 6e)
- Reduce minute ventilation by reducing respiratory rate and/or tidal volume. Remember that lowering the respiratory rate linearly reduces the mechanical power delivered to the lungs. (34597688)
- The mean airway pressure must be maintained high enough to keep the lungs recruited and oxygenated (this depends primarily on PEEP). The need to continuously oxygenate blood flowing through the lungs during VA-ECMO is discussed further in the section on mechanical ventilation settings to optimize oxygenation. ⚡️
- Sweep gas speed in the ECMO circuit is increased to provide adequate CO2 clearance.
How should the sweep gas speed be titrated?
- Best practice is unknown. Consequently, this needs to be tailored to each patient's needs (e.g., a patient with pulmonary hypertension wouldn't tolerate hypercapnia well).
- The pCO2 in the upper body is often ~5-15 mm higher than in the lower body (because it takes longer for CO2 generated in the upper body to reach the membrane lung). (38395004) Huge differences in pCO2 between the upper and lower body occur in patients with preserved native lung function and hyperventilation, neither of which is present here.
- Most authors recommend titration of sweep gas to target a high-normal pCO2 in the right radial artery. This prioritizes normalization of pCO2 to the lung, heart, and brain (while accepting mild alkalemia in the lower body). (34559091) Normalizing pCO2 in the upper body also has the advantage of suppressing the respiratory drive (which may improve ventilator synchrony and reduce sedation requirements).
- Exposure of the kidneys to alkalemic blood may stimulate bicarbonate excretion in the urine, producing a NAGMA (non-anion-gap metabolic acidosis). Exogenous bicarbonate repletion may be required to treat this NAGMA.
- Hypercapnia is generally well tolerated (e.g., permissive hypercapnia). Therefore, one might argue for targeting a low-normal pCO2 in the lower body and accepting mild hypercapnia in the upper body. In practice, there often isn't much difference between these strategies (either way, the pCO2 in the upper body will often be ~40-45 mm, and the lower body may be ~30-35 mm).

etCO2

VV ECMO

etCO₂ reflects pulmonary dead space.
etCO₂/paCO2 ratio >.83 is one parameter suggesting readiness to wean ECMO support. (35608503)

VA ECMO

etCO₂ reflects both pulmonary perfusion and pulmonary dead space.
etCO₂ <15 mm is sensitive for identifying native cardiac output <1 L/min, which suggestsLV dilation. (32962727)
etCO2 >34 mm predicts the ability to wean from ECMO. (41085892)
If passive leg raise causes a >12% increase in etCO2, it suggests fluid responsiveness with reasonable performance. (41261273)

pCO2 & pH goals

gradual CO2 reduction after ECMO initiation

For previously hypercapnic patients, CO2 must be decreased very gradually.
This is discussed above under the section on sweep flow.

goals in VV ECMO

This is really quite similar to usual pCO2 goals using a mechanical ventilator.
For patients with metabolic acidosis or alkalosis, it's often preferable to target a physiological pH (rather than a “normal” pCO2). (40047223)
Increased sweep speed may also be utilized to reduce respiratory drive (thereby decreasing dyspnea and ventilator dyssynchrony).

goals in pregnancy

PaCO2 is normally ~27-32 mm in pregnancy.
ELSO suggests targeting PaCO2 of 30-40 mm and pH >7.30 (40990339)
(Further discussion of normal blood gas parameters in pregnancy: 📖).

low circuit flow
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causes of low circuit flow

Preload inadequate (low P_ven): ⚡️
Membrane failure (elevated ▵P): ⚡️
Afterload is excessive (high P_Art, high P_Int, stable △P): ⚡️
Inadequate RPMs.

membrane lung dysfunction
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manifestations of membrane lung dysfunction may include:

[1] elevated ▵P and (▵P/V̇)

Interpreting ▵P:
- ▵P is usually 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)
Interpreting ▵P/V̇:
- ▵P/V̇ is arguably the best metric for the resistance of the membrane lung.
- If ▵P increases with a parallel increase in V̇, then this may not necessarily indicate worsening membrane lung dysfunction.
- There doesn't seem to be a specific cutoff value for ▵P/V̇ that indicates membrane lung dysfunction; instead, a progressive rise over time is worrisome.
Other findings may include:
- Rising P_Int with stable P_Art.
- Reduced V̇.

[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 before calculation (e.g., F_dO₂ set to 100%). However, it's dubious how much additional insight this calculation adds beyond considering the SarO2 and ParO2. 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 the 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 see only part of the membrane.
The 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 and requires membrane replacement. 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

The gas source is connected and turned on.
The 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 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 that it won't fix an elevated ▵P).
Increasing anticoagulation levels may stabilize worsening membrane dysfunction. (Schmidt 2022)
Replace the membrane or entire circuit.

systemic desaturation in VV ECMO
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SpO2 goal: discussed above ⚡️

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 S_vO₂.

The approach to systemic desaturation is as follows:

(#1) basic check of ECMO circuit and ventilator

F_dO₂ is set to 100%.
Sweep is functioning.
The tubing is connected correctly.
The mechanical ventilator is functioning correctly.

(#2) evaluate for membrane dysfunction

Bedside indicators:
- ▵P is >>50 mm.
- Blood in the return tubing isn't bright red.
Check the post-oxygenator P_arO₂ if in doubt. (34559091)
(See the section on membrane lung dysfunction: ⚡️)

(#3) evaluate for recirculation

diagnosis: signs of recirculation

Saturation shows a falling S_pO₂with a rising S_vO₂ (Taha 2024)
- S_vO₂ >75% (especially if this is rising without any distributive shock state).
- (S_pO₂ – S_vO₂) <10%.
  - If this difference becomes negative (i.e., S_vO₂ > SpO2), then recirculation is definitely occurring.
Visualization:
- Blood exiting and entering the patient may both appear bright red (a visual manifestation of the saturation gradient discussed above).
- The drainage cannula may show flashes of bright red blood. (Schmidt 2022)
Diagnostic/therapeutic trial of reduced V̇:
- Usually, reducing V̇ will decrease systemic oxygenation.
- If reducing V̇ by 5-10% causes a paradoxical improvement in peripheral oxygen saturation, this likely indicates recirculation. (33965970, 32197690)
Radiography may suggest cannula malposition:
- If two cannulas are used, placement within <8 cm suggests recirculation (the ideal distance may be ~8-13 cm). (Bagchi 2025) Alternatively, if two catheters are >8 cm apart, recirculation is rarely a problem. (41139354) However, some authors recommend keeping the catheters >10 cm apart, so this 8-cm cutoff isn't necessarily definitive. (33272724)
- 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.
- For patients with tricuspid regurgitation, inhaled epoprostenol may reduce pulmonary pressures and thereby improve forward flow of blood through the RV (rather than recirculating). (34559091)
- Reducing pump speed will reduce the recirculation fraction (and often improve systemic oxygenation).
Reposition catheter(s) if malpositioned:
- With two single-lumen catheters, target a separation distance of ~15 cm. (31632747)
- With a dual lumen catheter (e.g., Avalon) – make sure the 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)
Alter the ECMO circuit:
- Add another venous drainage catheter.

(#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 S_vO₂ (especially if S_vO₂ is <60%)

Some venous blood will always bypass the ECMO circuit. Consequently, increasing the venous blood saturation (S_vO₂) increases the systemic arterial blood saturation.
Potential interventions include:
- Reducing the systemic oxygen consumption (VO2): Discussed further above ⚡️.
- PRBC transfusion: Discussed further here ⚡️.

(#6) consider native lung deterioration

diagnosis

Chest radiograph shows pulmonary deterioration.
Impaired ventilator mechanics.

management may involve

Improve V/Q matching:
- Discontinue systemic vasodilators.
- Add inhaled pulmonary vasodilators.
Increased PEEP and potentially FiO2:
- Increasing PEEP may improve lung recruitment.
- Moderate increases in FiO2 (e.g., 60-70%) are likely safe.
- (With increased sweep speed and low respiratory rates, ventilator-induced lung injury and mechanical power administration to the lung are still kept at a minimum.)

weaning off VV ECMO
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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.

rough criteria to consider when initiating a weaning trial among intubated patients

Oxygenation:
- FiO2 consistently ≦60%.
- PEEP is relatively low (e.g., ≦10 cm for non-obese patients).
- PaO2 ≧70 mm.
Ventilation:
- Tidal volume <8 ml/kg IBW.
- Respiratory rate ≦28.
- Plateau pressure ≦28 cm and driving pressure <15 cm (if the patient is sufficiently passive on the ventilator to evaluate these accurately).
- ABG/VBG shows that both pH and PaCO2 are acceptable without excessive work of breathing.
- P0.1 is <5-10 cm (discussed further: 📖)
- Minute ventilation isn't severely elevated (suggesting a manageable amount of physiological dead space).
- etCO2/paCO2 ratio >.83 (35608503)
Imaging: Chest radiograph improved.

weaning from VV ECMO

Weaning may occur over 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 increased to a standard, lung-protective level of ventilator support. For example:
FiO2 may be increased to 30-60%.
Liberalize the respiratory rate to a usual rate (<30 b/min).
Pressure-regulated modes of ventilation: (33965970)
- Liberalize the 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 at >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 the goal of 1 L/min.
Check ABG with each decrement in the sweep gas flow rate.
Monitor saturation, pH, and work of breathing. (33965970)

[3] Off-sweep gas challenge

Turn off the sweep gas entirely for at least 2 hours (2-24 hours). (Red book 6e) The gas tubing should be clamped to prevent oxygen entrainment (analogous to apneic oxygenation). (Maybauer 2022) In a series of 192 off-sweep challenges, no significant changes were observed after 2 hours, suggesting 2 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:
- Oxygenation (saturation >88-92%; PaO2 >70-95 mm; FiO2 ≦60%).
- Ventilation (pH >7.3; pCO2 close to the patient's baseline).
- Absence of hemodynamic instability (e.g., arrhythmia, hypertension, hypotension).
- Absence of respiratory distress; p0.1 isn't very high. 📖 (33965970, Red Book 6e, Schmidt 2022)

[4] Decannulation

Confirm that off-sweep gas ABG shows PaO2 >70 mm and acceptable pH without excessive work of breathing.
The patient should be NPO (or, if a 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).
- The patient should have an active type & screen in case there is a 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) The risk of DVT may be >60%. Risk factors include the femoral site, larger cannula size, and less intense anticoagulation. (Red Book 6e)

RV dysfunction in VV ECMO
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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.
- (More on RV failure: 📖)
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, VV ECMO may be converted to VVA ECMO. However, the inability of VV ECMO to improve the RV is an ominous sign that points to a lack of recovery. (30865613)

systemic desaturation in VA ECMO
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[1] Make sure F_dO₂ is set to 100%, and the sweep is functioning.
[2] Is there differential hypoxemia? If so, see this section: ⚡️
[3] If saturation is low everywhere, consider membrane lung dysfunction: ⚡️

LV distension
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basics

risk factors for LV distension

Baseline LVEF <30%.
Mitral and/or (especially) aortic regurgitation.
VT storm.
Post-cardiac arrest.

adverse consequences of LV distension

[1] Bad for the LV:
- Over-distension is an explosive death spiral of the LV, wherein the LV falls entirely off the Starling Curve.
- Increased wall tension causes ischemia.
- If untreated, LV distension will prevent the LV from recovering.
[2] Thrombosis of the LV and/or LVOT. This is especially problematic for:
- Patients who are anticoagulated with bivalirudin (serum proteases degrade bivalirudin, so in the presence of high stasis, this may lead to low local concentrations of bivalirudin).
- Patients with a mechanical heart valve (or, to a lesser extent, recent mitral or aortic valve surgery). (34559091)
[3] Cardiogenic pulmonary edema with diffuse alveolar hemorrhage.
- This may also promote the development of pulmonary hypertension. (31530454)
[4] Sluggish blood flow through the lungs may cause blood exiting the aorta to be over-ventilated (with a low pCO2 and respiratory alkalosis).
[5] Loss of pulsatile blood flow is very problematic:
- Causes endothelial dysfunction (loss of pulsatile stress on the endothelial glycocalyx).
- Causes impaired microcirculatory perfusion. (40106084)

diagnosis of LV distension

Low pulse pressure, measured via A-line in the right arm.
- The pulse pressure should ideally be >10-15 mm. (31219839)
- Pulse pressure <10 mm suggests LV distension with poor function (although low LV preload is also possible, for example, due to right ventricular failure).
- ⚠️ Pulse pressure isn't reliable if there is an IABP in place.
etCO₂ <15 mm is sensitive 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 least once every 3 beats. Less frequent opening of the aortic valve indicates LV distension.
- [3] “Smoke” in the left ventricle indicates blood stasis & thrombosis risk.
- [4] At least moderate mitral regurgitation is usually present with LV distension. 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)
PCWP elevation. (34339398)

management of LV distension

⚠️ Achieving LV ejection as soon as possible is essential to avoid thrombosis within the left ventricle.

basic initial maneuvers

Ensure a perfusing rhythm (e.g., treat VT).
Ensure adequate anticoagulation. There is a very high risk of thrombus formation in the left ventricle. Until LV distension can be resolved, ensure the patient is fully anticoagulated.
Consider reducing the ventilator's minute ventilation (to prevent over-ventilation of blood flowing through the lungs).

reduce ECMO flow rate

This might be the most effective noninvasive strategy for treating LV distension. (34339398)
(Further discussion of ECMO flow: ⚡️)

increase 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 the patient is on pressors: Wean vasopressors.
- If the patient is not on pressors: Consider an arterial vasodilator or an inodilator. Afterload reduction is a desirable strategy because it reduces cardiac work (thereby decreasing myocardial ischemia).
Inodilator therapy:
- Initiate or up-titrate dobutamine (most patients with LV failure will need this).
- (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: device therapies for LV decompression

IABP:
- This may improve ejection & coronary artery perfusion.
- Meta-analyses suggest that IABP facilitates weaning from ECMO. (31530454)
- IABP may improve pulsatility, thereby improving endothelial integrity.
Impella:
- Impella may increase hemolysis (already a problem on ECMO) or limb ischemia (if both femoral arteries are cannulated).
(Surgical vent: a cannula inserted to drain blood (if centrally cannulated). This is connected to the venous return cannula. Vent flow should be monitored, as a decrease in flow can increase the risk of thrombosis.) (Bagchi 2025)
(Percutaneous transseptal venting of the left atrium, or balloon atrial septostomy.)

differential hypoxemia (aka north-south syndrome)
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epidemiology

Occurs in ~8% of patients on VA ECMO with peripheral cannulation.

cause

Three factors are 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 lung failure.
- (If the IVC is utilized for venous drainage, this may worsen matters by establishing dual-circuit circulation wherein blood tends to circulate within the upper body or lower body, with relatively little mixing between these areas).
The initiation of differential hypoxemia may reflect one of the following events:
- [1] LV recovery (in the context of ongoing lung failure).
- [2] 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 the brain and coronary arteries).

diagnosis: clinical findings

[1] Saturation & PaO2 in the right upper extremity are lower than in the lower extremities.
[2] NIRS (near-infrared spectroscopy) reveals inadequate regional oxygen saturation in the brain. ⚡️
[3] Venous drainage oxygen saturation (S_vO₂ ⚡️) may be unusually high.
Increased pulsatility in the arterial line tracing may be seen.
Ventricular arrhythmias may result from perfusing the heart with deoxygenated blood. (31219839)

treatments for differential hypoxemia

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):
- ⚠️ 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.
- [i] May decrease the power of a venting Impella.
- [ii] May decrease inotrope dose.
- [iii] Beta-blockers may be utilized to reduce endogenous cardiac output if excessive (although this raises a question of whether VA ECMO is still required). (Red Book 6e)
- [iv] May increase the ECMO flow (however, this could exacerbate cardiogenic pulmonary edema, so it's inadvisable). (Bagchi 2025)
Switch modalities or access points:
- If the heart has recovered but the lungs continue to fail, switch to VV ECMO.
- If the patient remains dependent on VA ECMO for cardiac support, 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 the body), added complexity, and increased likelihood of access complications. Individual flowmeters may be needed for both return catheters to avoid excessive flow return to the venous system. It may be challenging to achieve a high enough flow to perform both VV and VA ECMO simultaneously.
- The arterial return cannula may be repositioned to the axillary artery (although this carries a risk of hyperperfusion).
- Last-line intervention: convert to central aortic cannulation.

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 an arterial catheter in the femoral position.
- [2] The heart and lungs are working reasonably 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.

VA ECMO with central cannulation
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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 the body.
Nearly all patients receive an empiric LV vent.
There are no problems with differential hypoxemia.

VA ECMO in RV failure
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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 underfilled 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 the RV to eject is problematic:
- (a) Impairs perfusion & recovery of RV.
- (b) This may cause stasis & clots in the pulmonary vascular bed. Especially in the case of massive pulmonary embolism, this may cause catastrophic clot extension.
- (c) Inability to deliver drugs to the pulmonary vasculature.
Management may include:
- Inhaled pulmonary vasodilators.
- Inotropes to improve RV contractility.
- An intravenous pulmonary vasodilator may be considered.

weaning off VA ECMO
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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:
- Dobutamine <3 ug/kg/min.
- Milrinone <0.3 ug/kg/min.
- Norepinephrine <0.06 ug/kg/min.
- Epinephrine <0.1 ug/kg/min.
- Phenylephrine <1 ug/kg/min.
- Vasopressin <0.03 ug/kg/min. (34339398)
- (Another way to evaluate this: the Vasoactive Inotropic Score 🧮 should be <10.) (Red Book 6e)
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.
- Rising etCO2 may reflect increased native cardiac function and increased blood flow through the native lungs.
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 >10-12 cm.
- Lateral 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

Before decannulation, increase the ECMO flow rate and maintain anticoagulation (maintaining a higher ECMO flow during this period may help prevent circuit thrombosis).
Consider increasing vasoactive infusions slightly to provide a cushion in case hemodynamics deteriorate slightly. (34559091)
Once anticoagulation has worn off, decannulate.
Evaluate for complications:
- Neurovascular monitoring for arterial insufficiency.
- Ultrasound evaluation for DVT or arterial thrombus.

circuit flow arrest
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causes of circuit flow arrest

[1] Tubing problem:
- The clamp is left on (shortly after circuit initiation; check to ensure all clamps have been removed).
- Kink in tubing.
[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] Circuit air: ⚡️
- Arterial air alarm: The pump will stop if the arterial bubble detector senses air.
- Pump air lock: If the pump has been incompletely primed or has entrained a large amount of air, it will fail.

pump failure
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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

[1] Confirm that the pump isn't spinning.
[2] VA ECMO: Clamp the circuit to prevent backward flow that may cause a large arteriovenous shunt. (Schmidt 2022)
[3] Support the patient:
- Place the ventilator on emergency ventilator settings.
- Escalate vasoactives as needed (especially for VA ECMO).
[4] Try a hand crank or backup console (although this won't work for thrombosis or airlock).
[5] Pump head failure:
- Airlock: Try to de-air and eliminate the source of air.
- Thrombosis: Change the pump or the ECMO circuit.

circuit air
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definition

This refers to any air in the circuit.
Circuit air may range from a minor problem to a catastrophic problem (e.g., pump airlock; systemic air embolism in VA ECMO).

causes

Entrainment: air from the atmosphere.
- [1] A circuit breech pre-pump will suck air from the environment.
  - Crack in tubing or connector.
  - Loose connection.
- [2] Central or peripheral line near the drainage catheter that is left open or is leaking.
- [3] The drainage cannula was partially withdrawn.
- [4] Percutaneous tracheostomy with suction of air through the inferior thyroid vein.
Cavitation:
- Excessively negative pressure generates microbubbles.
Oxygenator:
- Oxygenator membrane rupture.
- Occlusion of the gas exhaust outlet. (Schmidt 2022)

manifestation

Bubble sensor alarm.
Air in the pump head may cause a distinctive sound.
A large volume of air may cause an airlock in the pump, resulting in immediate loss of ECMO support.
Air may be visible in the tubing.

**management of small amounts of air on the venous side**

Air can often be removed without stopping ECMO support.
If possible, venous air should be moved to the membrane lung using gravity (the membrane lung is the safest location to remove air).
Air may be withdrawn into a syringe or by removing the de-airing cap.

**management of a large amount of air in the circuit**

Immediate actions:
- Clamp out the circuit to prevent air embolization to the patient. (Taha 2024)
- The patient should be placed in the Trendelenburg position to direct any embolized air toward the legs. (Schmidt 2022) The left lateral decubitus position may also be helpful if possible. (32197690)
Try to identify and eliminate the source of air.
De-air the circuit if possible:
- Two-syringe technique.
- May remove the de-airing cap.
If the circuit cannot be rapidly de-aired, it may be necessary to replace it.

diagnosis & management of 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).
A CT brain should be obtained to evaluate for alternative pathologies. (31599814)
Treatment is supportive. Maximizing the FiO2 to decrease the nitrogen content of the blood may accelerate the reabsorption of emboli (treatment is discussed further here: 📖).

circuit disruption causing blood loss
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basics

Circuit disruption downstream of the pump will cause blood loss from the circuit, e.g.:
- Cracked luer locks or pigtail catheter.
- Loose caps or ports.
- Loose tubing – cannula connection.

clinical presentation may include

Drainage insufficiency.
Hypotension.
The flow sensor alarm may be activated.
Blood is leaking out of the circuit.

management

[1] Place clamps on both sides of the disruption to stop ongoing blood loss.
- Will likely need to separate from ECMO.
[2] Replace or repair the circuit.
[3] Transfusional support to replace lost blood.

circuit thrombosis
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thromboses with immediate risk

Large clot causing flow cessation/resistance.
Clot on the return side with risk of embolization to the patient.
Sufficient clot to cause failure of the membrane lung.

management

Isolate the clot to aspirate/remove.
May need to separate from ECMO and exchange the circuit.

emergent separation from ECMO
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reasons for clamping off ECMO

Disruption of circuit integrity:
- Large air entrainment.
- Circuit rupture.
- Accidental decannulation.
Pump failure.
Large clot.

approach

Clamp out:
- First, clamp the return tubing.
- Second, clamp the drainage tubing.
- Place clamps close to the patient (to isolate the patient from the circuit).
Drop RPMs to zero (to prevent hemolysis or cavitation).
Support the patient:
- VV ECMO: Maximize ventilator support.
- VA ECMO: Maximize ventilator support and escalate vasoactives.
Troubleshoot the problem and/or place the patient on a backup circuit.

cardiac arrest
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cardiac arrest on VV ECMO

General:
- Set F_dO₂ to 100%.
- Set the ventilator to rescue ventilator settings.
Manage per standard ACLS algorithms.

cardiac arrest on VA ECMO

Getting started:
- Set F_dO₂ to 100%.
- Set the ventilator to rescue ventilator settings.
If ECMO flow is >2 L/min and MAP >55:
- Hold compressions.
- Adjust vasopressors for the MAP goal.
- Evaluate & treat etiology.
If ECMO flow is <2 L/min and/or MAP is extremely low:
- Perform compressions.
- Perform ACLS (epinephrine, defibrillation, etc.)
- Troubleshoot loss of ECMO flow:
  - Drainage insufficiency?
  - Clamp on/kink?
  - Pump failure?
  - Massive clot?
  - Canula malpositioned?
  - Massive air entrainment?
  - Hypovolemia/hemorrhage?

arrhythmia
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arrhythmia on VV ECMO

Management is largely the same as for any patient.

arrhythmia on VA ECMO

immediate management

If ECMO support is sufficient, immediate defibrillation/cardioversion may not be needed.

etiologies to consider include:

Myocardial ischemia.
LV overdistension.
Excessive Impella flow (causing collapse of the LV).
Inotropic therapy.
Cannula malposition.

accidental decannulation
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Emergently separate from ECMO:
- Clamp out.
- Shut off RPMs.
Set the ventilator to rescue ventilator settings.
Hold pressure at the cannula site.
- [1] Risk of hemorrhage (especially if the catheter was in an artery).
- [2] Risk of ongoing air embolism (if the catheter was in a vein).
- [3] For arterial repair, consider consultation with a vascular or CT surgeon.
Significant blood loss: transfusion (activate massive transfusion protocol if appropriate).
Provide additional patient support as needed:
- Vasoactives for a patient on VA ECMO.
- For air embolization in VA ECMO, place the patient in reverse Trendelenburg.
Discontinue anticoagulation.
If ongoing ECMO support is required, arrange for insertion of a new cannula and reconnection to ECMO.

determining optimal anticoagulation intensity
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Anticoagulation intensity may be personalized based on the following factors.

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.
Hypercoagulable states (e.g., COVID-19, other infections).
Hypocoagulable states (e.g., postcardiotomy shock).

VV ECMO versus VA ECMO

VV ECMO doesn't carry a risk of ischemic stroke or intracardiac thrombosis, so a lower intensity of anticoagulation may be used. However, access-site DVT and PE risks 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, increasing the risk of thrombosis. (37763010)

flow rate & residence time

Higher flow rates require less anticoagulation (discussed above in the section on ECMO flow ⚡️).
Residence time is the average transit time of blood in the 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.

coagulation monitoring & targets
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core laboratory studies involved in coagulation monitoring (with targets)

Platelet count (& thrombocytopenia): ⚡️
Fibrinogen. ⚡️
INR. ⚡️
TEG. ⚡️
PTT. ⚡️
Anti-Xa level (only patients on heparin). ⚡️
Integrating anti-Xa & PTT to monitor heparin gtts. ⚡️

[1/7] 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 reducing platelet count, platelet dysfunction may also occur due to reduced levels of GP-Ib⍺ and GP-VI (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 the overall balance of hemostasis/thrombosis and clinical context.
50 b/L is a commonly used transfusion threshold for nonbleeding patients (especially those on therapeutic anticoagulation), although some protocols use a target of 30 b/L. (35080509, 38457000)

[2/7] fibrinogen

Generally, target >~100 mg/dL if there is no bleeding. (35080509)
Generally, target >150 mg/dL if active hemorrhage is present. (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 falsely low in patients who are receiving DTIs. (32371744) TEG may be preferred in that situation (although standard TEG assays don't provide an isolated measurement of fibrinogen level 📖). (38337414)

[3/7] INR

INR correlates poorly with clinical bleeding in complex coagulopathies (e.g., DIC, cirrhosis, sepsis, ECMO).
Some sources recommend using FFP to “correct” an elevated INR, but there is no evidence to support this. (38457000) Consequently, usual algorithms for FFP transfusion in critically ill patients without ECMO may be applied. (38457000) TEG may help determine whether enzymatic coagulation is genuinely compromised or has been rebalanced.
⚠️ INR may be prolonged by DTIs (direct thrombin inhibitors). (36703184)

[4/7] TEG (thromboelastography)

basics

TEG is a whole-blood, integrative coagulation assay (discussed 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 PTT. This makes the R-time sensitive to heparins, direct thrombin inhibitors, or deficiencies in the intrinsic coagulation system (VIII, IX, XI, and XII). (36108651)
Comparing R-time with and without heparinase allows 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 to heparin titration to target a TEG-5000 R-time of 16-24 minutes. Clinical outcomes were similar, but, as a pilot study, the results 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 flat-line TEG tracings, the median anti-Xa level was 0.36 IU/mL (within the therapeutic range). 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).

[5/7] PTT

uses

[1] PTT is the primary laboratory test to titrate DTIs (direct thrombin inhibitors). Unfortunately, PTT may underestimate the actual anticoagulant effect of DTIs at higher drug concentrations. (35080509)
[2] PTT may be used to evaluate the level of UFH:
- PTT evaluates coagulation more globally (including the heparin effect and other coagulation factors).
- PTT may be the most accurate as a global indicator of bleeding risk rather than of heparin efficacy. Supratherapeutic PTT levels correlate with clinical bleeding. (31045921)

values

Normal PTT is ~25-35 seconds.
Factors that commonly affect PTT:
- PTT is increased by: coagulation factor deficiency, hepatic dysfunction, lupus anticoagulants, and consumptive coagulopathies.
- PTT is reduced by: hyperfibrinogenemia, elevated factor VIII levels, and other acute-phase reactants.
Target in heparin anticoagulation:
- 50-70 seconds or 2-2.5 times the midpoint of the normal range is recommended by ISTH ECMO guidelines. (36700496)
- 40-60 seconds may be adequate for VV ECMO and also in pregnancy. (Red Book 6e; recommended target for VV ECMO by Rodriguez et al.; Maybauer 2022; 40990339)
- >75 seconds may correlate with an increased risk of hemorrhage. (31045921)
- (Anti-Xa versus PTT to monitor heparin is discussed further in the section below. ⚡️)
Target with direct thrombin inhibitors (bivalirudin, argatroban):
- Generally, the same target ranges are used as with heparin. (listed above).(36700496, Maybauer 2022)
- A baseline PTT should be obtained before initiation. If the baseline PTT is unusually low or high, the target PTT may need to be adjusted accordingly.
  - In general (not specifically for ECMO patients): The PTT target is generally 1.5-2.5 times (bivalirudin) or 1.5-3 times (argatroban) of the patient's own baseline value (but usually not above 100 seconds). (25260718, 22315270, Erstad 2022, Sedhai et al 2020, FDA argatroban label)
  - ISTH ECMO guidelines recommend targeting 50-70 seconds or 2-2.5 times the normal level with argatroban. (ISTH ECMO guidelines 36700496; 37763010)
- (Further discussion in the chapter on anticoagulants here: 📖)

[6/7] anti-Xa level

Anti-Xa level is a direct measurement of the effect of heparin on coagulation. It is utilized only to titrate unfractionated heparin.
Anti-Xa level does not represent the patient's overall hemostatic balance. (38671589)
Anti-Xa level may be the best indicator of heparin efficacy. Subtherapeutic anti-Xa levels correlate with clinical thrombosis. (31045921)
Falsely low anti-Xa occurs with: (35080509)
- Plasma-free hemoglobin >50 mg/dL. ⚡️
- Triglycerides >500 mg/dL. (36703184)
- Bilirubin >6 mg/dL.
- Methylene blue therapy.
Target anti-Xa level:
- 0.3-0.7 IU/ml is the usual target for therapeutic anticoagulation in general.
- 0.3-0.5 IU/ml is recommended by ISTH ECMO guidelines. (36700496)
- 0.2-0.3 IU/ml was utilized for VV ECMO in the EOLIA trial. (29791822)
- 0.2-0.4 IU/ml is recommended in pregnancy by ELSO. (40990339)

[7/7] integration of anti-Xa & PTT for monitoring of heparin anticoagulation in patients on mechanical support (including ECMO & Impella)

Discussed further here: 📖

DIC
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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. 📖
Utilization of D-dimer?
- Elevation of D-dimer is nonspecific, but markedly elevated values have greater significance.
- Elevation of D-dimer levels may reflect DIC or clot formation in the pump or oxygenator (suggested by steady increases in D-dimer). (36703184)

treatment of DIC

[1] Manage the cause if possible:
- If membrane thrombosis is causative, replace 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: 📖)

acquired von Willebrand syndrome (AVWS)
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pathophysiology of vWF

The normal functions of von Willebrand factor include:
- [1] A bridge between damaged blood vessels and activated platelets (through the GPIb receptor).
- [2] Carrier for factor VIII (significantly increasing the half-life of factor VIII). (Maybauer 2022)
High shear forces during ECMO deplete high-molecular-weight von Willebrand factor multimers. (28898902, Red Book 6e) This causes acquired von Willebrand syndrome (AVWS type 2A).

epidemiology

Almost all ECMO patients develop partial or complete loss of vWF high-molecular-weight multimers within a few hours of ECMO initiation. (38925492)

clinical manifestations may include

Diffuse hemorrhage.
Sudden mucosal bleeding. (38747332)
Unexpected bleeding after minor surgery. (Maybauer 2022)

laboratory analysis & diagnosis

AVWS doesn't affect most coagulation studies (e.g., conventional coagulation tests, TEG).
The diagnosis can be made based on a reduced vWF activity relative to vWF antigen. However, this is essentially impossible to measure in practice (due to delayed turnaround time).
PFA (platelet function analyzer) is highly sensitive but not specific for the loss of vWF high-molecular-weight multimers. 📖 Additionally, the PFA is not valid if the platelet count is <80,000/uL or the hematocrit is <30% – conditions frequently encountered among ECMO patients. (15982339)
Epidemiological studies show that AVWS occurs in nearly all patients on ECMO. So it's dubious whether laboratory testing is necessary – you can assume that the patient has AVWS. (38925492)

treatment

Treatment may be considered in the face of persistent or life-threatening bleeding (based on the assumption that AVWS may be contributing to the net state of anticoagulation). However, there is no high-quality evidence to support this. Unfortunately, any strategy to deliver vWF will be limited by ongoing vWF consumption.
DDAVP may transiently increase vWF levels. This was found to be ineffective in one study involving COVID-19 patients. However, the generalizability of this study may be limited by endothelial vWF depletion observed in COVID. (38925492)
Cryoprecipitate can be used to replete vWF and VIII levels. This hasn't been studied as a specific therapy for AVWD in ECMO patients. However, it might be a theoretical argument to favor the use of cryoprecipitate over fibrinogen concentrates as a therapy for hypofibrinogenemia among bleeding ECMO patients.
Antifibrinolytics (e.g., tranexamic acid or aminocaproic acid) have demonstrated efficacy for other etiologies of von Willebrand Disease 2A, but this hasn't been evaluated in ECMO patients. This could be considered for refractory, life-threatening bleeding in the absence of better options. (39133377)
vWF levels recover quickly after discontinuation of ECMO. (Red Book 6e)

HIT (heparin induced thrombocytopenia)
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epidemiology

The incidence might be ~5%. This is an uncommon but real complication. (Red Book 6e)

diagnosis

Diagnosis is challenging because both thrombocytopenia and thrombosis are common in ECMO.
Clues to a diagnosis of HIT may include falling platelet counts and circuit thrombosis. (38747332)
The 4T score 📖 appears to have adequate sensitivity (a score of 0-3 excludes HIT). However, the 4T score may have impaired specificity. (32232501)
Definitive diagnosis relies upon detecting 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 about HIT, anticoagulation should be transitioned to a non-heparin agent (bivalirudin or argatroban) while the evaluation is ongoing.
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: 📖).

bleeding
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common sites of bleeding

Cannulation sites are the most common. (Taha 2024)
Other 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 numerous coagulopathies

Primary hemostasis is often profoundly impaired (explaining the tendency for mucosal bleeding):
- Acquired von Willebrand syndrome ⚡️
- Thrombocytopenia.
- Platelet dysfunction:
  - [i] Uremic platelet dysfunction.
  - [ii] Medication-related (e.g., aspirin, P2Y12 inhibitors).
  - [iii] Platelet dysfunction is caused by the loss of glycoproteins Ib⍺ and VI receptors on platelets due to exposure to high shear stress in the ECMO circuit. (37519116)
Secondary hemostatic abnormalities:
- Anticoagulation (e.g., heparin or bivalirudin).
- DIC causes a consumptive coagulopathy (e.g., hypofibrinogenemia).

hemorrhage management

evaluation of coagulation status

Complete blood count.
INR, PTT, fibrinogen level.
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).
- Topical hemostatic agents may be helpful for superficial bleeding.
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 the risk of circuit thrombosis.
Address other coagulopathies:
- Cryoprecipitate to target fibrinogen levels >150-200 mg/dL.
- Platelet transfusion for target >50 b/L.
- Calcium administration for significant hypocalcemia.
- FFP may be considered (e.g., if the heparinase-TEG reveals a pathologically 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 supporting its use.
- Uncontrollable, life-threatening bleeding has been treated successfully with antifibrinolytics (aminocaproic acid or tranexamic acid). However, due to the risk of circuit thrombosis, this should be utilized only for refractory hemorrhage. (Schmidt 2022)

optimal hemoglobin
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general comments on transfusion targets

Hemoglobin >7 g/dL is adequate for most patients. (38999360)
Hemoglobin >8 g/dL is a reasonable target in the setting of active myocardial ischemia.
Blood transfusion to target a hemoglobin of 10 g/dL may occasionally be used to improve oxygen delivery (DO2). However, this should ideally be avoided, given evidence that a restrictive transfusion strategy may improve outcomes. (28704244)

risks & drawbacks involved in RBC transfusion

Viscosity: A higher hemoglobin level increases blood viscosity, which may impair flow through the circuit and the body.
Intravascular hemolysis: A higher hemoglobin level may increase intravascular hemolysis, with downstream complications from that process (e.g., renal failure, hypercoagulability).
Coagulation: A higher hematocrit will increase the tendency of blood to clot (usually undesirable, but this may be desirable for patients with ongoing hemorrhage).
ARDS risk.
Volume overload risk (TACO).
Alloimmunization (may be especially problematic for patients who require organ transplantation).
Limited O2 delivery from transfused erythrocytes: It's unclear whether transfused blood truly improves oxygen delivery to the tissues. (Schmidt 2022)
Immunosuppression.

hemolysis
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causes of hemolysis

Excessive circuit pressures:
- P_Ven <-100 mm ⚡️; tubing chatter.
- P_Art >250 mm. ⚡️
- High circuit flow rates. ⚡️
- Kinked or intentionally split tubing. (Schmidt 2022)
Clot in the circuit:
- Pump head thrombosis (occurs in <4% of cases but may cause sudden and massive hemolysis). (34339398)
- Membrane lung dysfunction. ⚡️
The heat exchanger 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) Without an alternative explanation, it is concerning for circuit-derived hemolysis. (Schmidt 2022)
- >100 mg/dL indicates severe hemolysis and 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):
- The chemistry laboratory routinely measures this index to assess specimen hemolysis. It is calculated by measuring plasma hemoglobin via spectrophotometry, so it is fundamentally a measure 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. (38611592)
- 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 happen with minor Foley trauma). For anuric patients on dialysis, the dialysis effluent may turn pink. (Taha 2024)
- 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 suggests hemolysis (but LDH correlates poorly with plasma-free hemoglobin).
- Falling hemoglobin.

consequences of hemolysis

[1] Acute kidney injury.
[2] Thrombosis (activates platelets).
[3] Nitrogen oxide depletion increases vascular tone.
(It also interferes with the colorimetric anti-Xa assay. ⚡️)

epidemiology

One series found that plasma-free hemoglobin >50 mg/dL 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 in VV ECMO. (Red Book 6e)

management

Circuit pressures & tubing chatter must be decreased:
- If possible, reduce the circuit flow rate.
- Remove any kinks in the tubing.
- Further discussion on the management of P_Ven: ⚡️
- Further discussion on the management of P_Art: ⚡️
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 the heat exchanger if it malfunctions. (Schmidt 2022)
Anemia may require PRBC transfusion (discussion of target hemoglobin: ⚡️).

pericardial tamponade
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epidemiology

Percardial tamponade occurs in 2.5% of ECMO patients, with VA ECMO accounting for 80% of these. (38233245)
Etiologies may include cannula placement with myocardial perforation, rib fractures from CPR, and/or anticoagulation. (32197690)
This is actually similar to the rate of pericardial tamponade seen following cardiac surgery, which underlies the need for a high index of suspicion for this (especially in VA-ECMO patients).

manifestations

Hypotension (may initially respond to fluid resuscitation).
Narrow pulse pressure (or complete loss of pulsatility in the context of VA ECMO).
Venous return insufficiency can occur (pericardial pressure collapses the right atrium, which impairs blood flow into the venous drainage cannula from the upper body).

diagnosis

Echocardiography is the central modality.
Tamponade physiology may be more challenging to discern in the context of ECMO.

pulmonary complications
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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:
- The risk of venous thromboembolic disease is exceptionally high.
- Systematic screening shows that DVTs occur at the cannulation site in ~50% of patients (risk is higher in VV ECMO as compared to VA ECMO). (41139354)
- The risk of PE is lower, perhaps ~20%.
Diagnosis:
- Ultrasonography is the test of choice for evaluating 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 adjusting the intensity of anticoagulation).
- 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: 📖)

gastrointestinal issues
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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 was historically considered a contraindication to enteral nutrition due to concerns about mesenteric ischemia. However, recent evidence has allayed these fears, suggesting instead that enteral nutrition might reduce the risk of mesenteric ischemia. (33609105, 30030574) Following initial resuscitation and stabilization on VA ECMO, enteral nutrition appears to be safe and beneficial.
Indirect calorimetry isn't possible on ECMO because the membrane lung removes CO2. Consequently, caloric needs should be estimated based on weight (e.g., 25 kCal/kg). (Taha 2024)
Total parenteral nutrition may cause problems due to infused lipids accumulating in the membrane lung. Enteral nutrition is preferred whenever feasible.
(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) are more effective than H2-blockers (a 0.5% absolute reduction in clinically significant gastrointestinal hemorrhage based on the PEPTIC trial). (31950977)

AKI (acute kidney injury)
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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 nephrotoxic agents whenever 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 by accessing the ECMO circuit. When possible, it's preferable to keep hemodialysis separate from the ECMO circuit to keep the ECMO circuit as simple as possible and facilitate troubleshooting.

neurological complications
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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:
- [1] CNS hypoperfusion prior to cannulation (the most common cause).
- [2] Differential hypoxemia. ⚡️
- [3] Cardiac arrest.
- [4] CO2 dysregulation and cerebral vasoconstriction. (31599814)

management

[1] Post-arrest treatment involves standard resuscitative pathways (including targeted temperature management). The ECMO circuit may be used to control temperature, eliminating the need for additional 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 venous sinus thrombosis. (31599814)
- CT perfusion may be considered while the patient is at the scanner (given how difficult it is to mobilize ECMO patients to a CT scan).

management

Revascularization options: 📖
- IV alteplase is contraindicated in ECMO. (31599814, 39620302)
- Mechanical thrombectomy may be performed for large vessel occlusion.
Anticoagulation & investigation of the cause of the stroke:
- In VA ECMO, check the circuit for thrombosis, and 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 strokes, holding anticoagulation for a few days may be considered. (31599814)
Blood pressure: Non-ECMO patients with new acute ischemic stroke who aren't undergoing intervention should be allowed to have permissive hypertension up to 220/120 mm to promote perfusion of the ischemic penumbra. However, this is often neither safe nor achievable in the context of ECMO.
- VA ECMO: Cardiac function often cannot tolerate excessive afterload, so very high blood pressures cannot be tolerated. (39620302)

cerebral air embolism

See the section above on circuit air: ⚡️

ICH (intracranial hemorrhage)

epidemiology

The risk is ~4%. (33814895)
Most ICHs appear shortly after ECMO cannulation. (33814895)
Risk relates largely to anticoagulation and/or consumptive coagulopathies. Specific risk factors include:
- Thrombocytopenia, in particular, is a risk factor.
- Anticoagulant and antiplatelet use.
- Bloodstream infections.
- Rapid reduction of pCO2 (which may cause an ischemic area with subsequent hemorrhagic transformation).
- Renal failure, dialysis. (31599814, 33814895)
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.
Differential diagnosis: residual contrast from a recent iodinated contrast-enhancing procedure (E.g., cardiac catheterization or cerebral angiography). (41139354)

management

Anticoagulation must be held and potentially reversed (although reversal may carry high risks of membrane lung thrombosis). ECMO circuit flow may be increased to reduce the risk of circuit thrombosis. How long to hold anticoagulation depends on patient specifics. Close monitoring for evidence of thrombosis may also guide management (e.g., visual inspection for thrombi and circuit pressures). (33814895)
Platelet counts should be maintained at>50,000. (Red Book 6e)
Blood pressure control to reduce hematoma expansion.
Related topics:
- Hematologic investigation and management of bleeding on ECMO: ⚡️
- General management strategies for intracranial hemorrhage: 📖

CVST (cerebral venous sinus thrombosis)

CVST may be associated with large-bore jugular cannulas, which cause venous hypertension.
Manifestations are various (e.g., headache, seizure, encephalopathy).
Diagnosis is based on CTV (CT venography).
Management:
- Anticoagulation (which patients are on anyway).
- Acetazolamide may be considered to reduce intracranial pressure.
- Endovascular mechanical thrombectomy may be considered. (39620302)
- (More on CVST management: 📖)

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 isn't sequestered substantially (<10% protein binding, LogP -0.6). (31599814)

limb ischemia
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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 leads 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).
NIRS (near-infrared spectroscopy) may be helpful. ⚡️
Ultrasound evaluation (spectral Doppler ultrasound may evaluate blood flow, compared to the contralateral limb, to account for changes in left ventricular ejection). (25296619)
CT angiography with runoff can be definitive.

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.

approach to infection in an ECMO patient
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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, 38442737)
Microbial culture data is often essential (however, sorting out infection versus colonization may remain confounding).
It's often unclear how precisely to define infections in patients on ECMO. (38442737)

common sites of infection

Pre-existing infection before ECMO initiation (e.g., community-acquired pneumonia).
VAP (ventilator-associated pneumonia) is the most common infection among patients on VV ECMO. (38442737)
Line infection (including cannula sites).
- The risk of cannula insertion site infection was 14% in the EOLIA trial. (29791822) Risk increases linearly related to the duration of therapy. (35326801)
- Directly accessing the circuit for cultures isn't recommended, as this may risk contaminating the circuit. (38442737)
- Treatment:
  - Initial therapy involves antibiotics. Follow blood cultures to determine if the blood can be sterilized. If positive blood cultures persist, replacing the ECMO circuit may be necessary. (Taha 2024) Additional investigation for endocarditis and other device- or line-related infections may also be appropriate.
  - If infection is persistent and uncontrolled, removing the ECMO cannulae and inserting fresh cannulae at different sites may be necessary.
  - Antibiotics generally need to be continued until after decannulation. (38442737)
Surgical site infection.
Urinary tract infection (although it's often difficult to differentiate infection from colonization; discussed further here: 📖).
C. difficile. (38442737)

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.

antibiotic pharmacology in ECMO

Discussed below ⚡️

ECMO pharmacology
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general approach for determining the 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 rough guide for medications whose ECMO pharmacology hasn't been well investigated.

major pharmacologic issues in ECMO

[1] Increased volume of distribution (affects hydrophilic medications with a low Vd):
- This results from the increased blood volume in the circuit.
[2] Sequestration (primarily affects highly lipophilic and protein-bound drugs):
- Drugs adhere to the plastic of the 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] Low albumin levels (affects highly protein-bound drugs):
- Albumin levels may decrease due to protein adsorption onto the circuit.
- Lower albumin levels may increase free drug levels.

general strategies for optimizing pharmacokinetics

Select a more hydrophilic drug, if possible.
If possible, select medications with a wider therapeutic index (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).

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 give this on a scheduled basis (rather than PRN).

opioids

Pharmacokinetic summary:
- 🏆 Hydromorphone: 10% protein binding; LogP 0.9 (Taha 2024)
- Fentanyl: 80-85% protein binding; LogP 4.1
- Morphine: 30-40% protein binding; LogP 0.9
Hydromorphone:
- Low lipophilicity and protein binding.
- Generally, it is a preferred opioid for ECMO patients. (Taha 2024)
- Hydromorphone has a relatively long half-life so that it may be dosed PRN.
- Some studies suggest that the 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). It is the most sequestered of all three commonly utilized opioids. (Taha 2024)
Morphine: Pharmacokinetically, morphine is reasonably good. However, histamine release and accumulation of active metabolites in renal failure limit its use. (Taha 2024)

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 that higher doses may be required. It is unclear how to balance the need for higher doses with the minimization of propofol infusion syndrome.
Propofol may remain useful for procedural sedation and short-term sedation. (Taha 2024)

central alpha-2 agonists

Dexmedetomidine infusion: 💉
- Pharmacokinetics: 94-97% protein binding; LogP 3.39 (Taha 2024)
- The circuit will substantially adsorb dexmedetomidine. Higher doses 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: ~35-47% protein binding; Log P ~3.
The circuit may absorb ketamine, leading to lower drug levels. However, numerous studies describe the successful use of ketamine among patients on ECMO.

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 helpful for procedural sedation.
Benzodiazepines are not generally preferred agents in the ICU due to the 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 emergencies. 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 the 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 managing some patients with persistent agitated delirium refractory to more commonly used 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, caution is required when measuring total valproate level since the free level may be proportionally higher among patients with hypoalbuminemia).

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 helpful agent for adjunctive sedation in the context of ECMO. (Curran et al.)
A major limitation of phenobarbital is that it induces cytochrome P450 enzymes with numerous drug-drug interactions. This could further complicate pharmacokinetics, especially among patients taking a wide range of medications.

paralytics

Pharmacokinetics:
- Cisatracurium: LogP -3.73, 38% protein binding.
- Rocuronium: LogP -1.68, 46% protein binding.
- Vecuronium: LogP -0.75, 70% protein binding. (Taha 2024)
Cisatracurium is the best agent for ongoing paralytic infusions. Its clearance isn't affected by renal or hepatic dysfunction, which is common among patients on ECMO. Cisatracurium has lower lipophilicity than rocuronium or vecuronium, so it likely has lower ECMO sequestration. Cisatracurium may also have a lower rate of neuromuscular complications than aminosteroid paralytics (rocuronium, vecuronium).
Paralysis should be closely monitored using a train-of-four and titrated to effect.

antibiotics

Below are antibiotics that are more useful for patients on ECMO. Hydrophilic antibiotics have the most predictable pharmacokinetics, although they have an increased volume of distribution (due to the ECMO circuit volume).

beta-lactams

Ampicillin 🟢 💉 (20% protein binding; Vd 0.25 L/kg; LogP -1.1). The higher end of standard dosage appears to achieve therapeutic targets, but available clinical data are sparse. (37243488)
Nafcillin 🟠 💉 (90% protein binding; LogP 2.9). It may be sequestered by the ECMO circuit. Dose on the higher end of the normal dosing range. (39367501)
Cefazolin 🟡 💉 (80% protein binding; Vd 0.2 L/kg; LogP -0.6) Standard dosing is probably adequate, but some in vitro data suggest ~20% loss to the circuit. Dose on the aggressive side of the standard dosing range. (31610538, 35326801, 39367501)
Ceftazidime 🟢 💉 (15% protein binding; Vd 0.3 L/kg; LogP -1.6). Pharmacokinetics are unaffected by ECMO. (35326801)
Ceftriaxone 🟢 💉 (90% protein binding; Vd 0.2 L/kg; LogP -1.7). Standard dosing appears to achieve therapeutic targets. In a prospective study involving 14 patients, ECMO didn't influence ceftriaxone pharmacokinetics. (35253107) Dose on the higher end of the normal dosing range. (35253107; 29732181, 39367501)
Cefepime 🟢 💉 (20% protein binding, Vd 0.3 L/kg; LogP -0.1). It is unlikely to be affected by ECMO, with validation in patient PK samples. (39367501)
Ceftaroline 🟢 💉 (20% protein binding; Vd 0.3 L/kg; LogP -0.8 to 2.3). It is unlikely to be affected by ECMO, but little data exists regarding clinical use. Kim et al. suggest increasing the dose to 600 mg q8hr. (39367501)
Piperacillin-tazobactam 🟡 💉 (30% protein binding; Vd 0.3 L/kg; LogP 0.5). The data is somewhat conflicting. Dose on the higher end of a normal dosing range (ideally with extended infusion). (29732181, 34460303, 33569597, 39367501)
Ertapenem: 🔴 💉 (90% protein bound, LogP 0.3). Data is lacking; use meropenem instead. (39367501)
Meropenem 🟢 💉 (2% protein binding; Vd 0.35 L/kg; LogP -0.7). Dosing is similar to other critically ill patients, with several studies showing no change in pharmacokinetics due to ECMO. (29732181, 35326801, 34460303)

other antibiotics

Azithromycin 🟢 💉 (7-51% protein bound; LogP 3-4): Use standard doses. A case series demonstrated minimal effect on pharmacokinetics. (39367501)
Doxycycline 🟡 💉 (80% protein binding; Vd 0.75 L/kg; LogP 0.6). Data is limited, but one case report found adequate pharmacokinetics. (Mehta et al.) Kim et al. recommend using standard doses. (39367501)
Linezolid 🟠 💉 (30% protein binding; Vd 0.6 L/kg; LogP 0.7). Despite hydrophilicity, some case reports describe inadequate levels when using linezolid. (32426841, 35326801, 33239110, 23453617) Ceftaroline might be preferable for the therapy of MRSA pneumonia. Kim et al. recommend considering a dose of 600 q8hr or an alternative agent for severe infection or if a suboptimal response is noted. (39367501)
Daptomycin 🟢 💉 (90% protein bound; LogP -5). Data suggest minimal effects on PK (including a prospective study with 36 patients). (38814793) Standard doses may be used. (39367501)
Metronidazole 🟢 💉 (20% protein binding; Vd 0.7 L/kg; LogP -0.18). Unlikely to be affected by ECMO.
Trimethoprim-Sulfamethoxazole 🟠 💉 (Sulfamethoxazole is 70% protein bound with LogP of 0.9; trimethoprim is 44% protein bound with LogP of 0.9). Little data is available (a single case report showed adequate pharmacokinetics). (39367501) The dose of trimethoprim-sulfamethoxazole is controversial, with traditional doses being unnecessarily high (e.g., 15 mg/kg/day for Pneumocystis). As such, using a traditional dose is likely to achieve adequate levels.
Fluoroquinolones 🟢 💉
- Ciprofloxacin (30% protein binding; Vd 2.5 L/kg; LogP -1.1).
- Levofloxacin (30% protein binding; Vd 1.1 L/kg; LogP -0.4).
- Fluoroquinolone concentrations remain therapeutic with standard dosing, but fluoroquinolones aren't usually preferred in the ICU. (29732181, 35326801)

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). The volume of distribution is often increased, but the circuit doesn't absorb aminoglycosides. Close monitoring should be utilized. The primary drawbacks are nephrotoxicity and limited penetration of some 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) Kim et al. recommend using a loading dose of 12 mg/kg or double the usual treatment dose, followed by standard treatment doses. (39367501)
Voriconazole 💉 (60% protein binding; LogP 1.5). Significant drug adsorption to the circuit seems to occur (71% circuit drug loss in one report). (29732181) Kim et al. suggest increasing the loading dose duration (e.g., 6 mg/kg q12 for two days) and then reducing the dose to 3-4 mg/kg. Drug levels should also be followed. (39367501)
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 -1.6). 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. (39367501)

ECMO radiology
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There are innumerable possible ECMO configurations. The following discussion refers to the most common ones.

VV ECMO with two cannulas

femorojugular configuration

Venous drainage cannula: The distal tip is below the IVC/RA junction, near the hepatic vein.
Arterial return cannula: Distal tip at the SVC/RA junction.
(The optimal distance between catheters is discussed in the section on recirculation here: ⚡️).

(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)

The return port is within the RA, pointed toward the tricuspid valve. If the arterial outflow (seen as a slight discontinuity on the cannula) points 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 the IVC and the 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.)

candidacy for ECMO
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patient selection for VV ECMO

VV ECMO is a bridge to either:

Recovery of native lungs (most patients).
Lung transplant. (33965970)

contraindications to VV ECMO

[1] Irreversible lung injury plus ineligible for transplant (absolute contraindication).
[2] CNS pathology:
- Central nervous system hemorrhage.
- Irreversible and incapacitating central nervous system pathology.
[3] Non-correctable coagulopathy/bleeding:
- Contraindication to anticoagulation (e.g., severe coagulopathy).
[4] Mechanical ventilation for >7 days with Pplat >30 cm and FiO2 >90%. (33965970)
[5] Global considerations:
- Severe, acute multiorgan failure (especially if respiratory failure is unlikely to drive the overall outcome).
- Pre-existing life-limiting disease (e.g., advanced malignancy).
- Age >75 years old, especially with declining baseline functional status (increasing risk of death with increasing age; no strict cutoff threshold is established).
- Severe immunosuppression.

general indications for VV ECMO

Hypoxemic respiratory failure:
- General indication: P/F <80 mm after optimal medical management, including a trial of prone positioning (if possible).
- EOLIA trial criteria include the following (despite optimization, including measures such as paralysis, proning, and inhaled pulmonary vasodilators). (38999360)
  - P/F <50 for >3 hours, on FiO2 >0.8%.
  - P/F <80 for >6 hours, on FiO2 >0.8%.
Hypercapnic respiratory failure:
- pH <7.20-7.25 with PaCO2 >60 mm despite optimal conventional mechanical ventilation (respiratory rate 35 b/m and plateau pressure ≦30-32 cm).
Lung transplantation: Support as a bridge to lung transplantation or primary graft dysfunction following lung transplantation. (33965970)

situations where VV ECMO may be beneficial

Common indications:
- ARDS, including various etiologies such as:
  - Severe pneumonia.
  - Aspiration.
  - Thoracic trauma (e.g., traumatic lung injury and severe pulmonary contusion).
  - Acute eosinophilic pneumonia.
- Status asthmaticus.
- Massive air leak syndromes (e.g., large bronchopleural fistula). (38999360)
- Severe inhalational injury.
Other indications may include:
- 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)
- Peri-lung transplant (e.g., primary lung graft dysfunction and bridge to transplant). (33965970)
- Complex airway management.

scoring systems

The RESP score may be utilized to predict mortality. 🧮

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 is 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 inform decision-making before ECMO.
- SAVE score predicts survival after VA ECMO (MDCalc: 🧮).

questions & discussion
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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

24977195 Chung M, Shiloh AL, Carlese A. Monitoring of the adult patient on venoarterial extracorporeal membrane oxygenation. ScientificWorldJournal. 2014;2014:393258. doi: 10.1155/2014/393258 [PubMed]
25296619 Lee S, Chaturvedi A. Imaging adults on extracorporeal membrane oxygenation (ECMO). Insights Imaging. 2014 Dec;5(6):731-42. doi: 10.1007/s13244-014-0357-x [PubMed]
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Books

MacLaren, G. (2022). Extracorporeal Life Support: The ELSO Red Book 6th Edition.
Maybauer, M. O. (2022). Extracorporeal membrane oxygenation: An Interdisciplinary Problem-Based Learning Approach. Oxford University Press.
Schmidt, G. A. (2022). Extracorporeal membrane oxygenation for adults. Springer Nature.
Taha, A. R. (2024). ECMO: A practical guide to management. Springer. 38747332

CONTENTS

parameters

management common to VV & VA ECMO

management unique to VV ECMO

management unique to VA ECMO

🚨 ECMO emergencies 🚨

hematology of ECMO

other topics

RPM & flow(back to contents)

RPM & flow

pump speed (RPM)

RPMs in VV ECMO

RPMs in VA ECMO

V̇ (ECMO blood flow)

ECMO flow & general maximization of safety

ECMO blood flow in VV ECMO

ECMO blood flow in VA ECMO

intravascular pressures(back to contents)

intravascular pressures

hemodynamic monitoring on VV ECMO

key differences include

hemodynamic monitoring in VA ECMO

evaluation of native cardiac output (COnative)

indicators of perfusion

indicators of preload

indicators of preload responsiveness

Pven (venous pressure) & drainage insufficiency

causes of excessively negative Pven (aka drainage insufficiency)

management of drainage insufficiency

PInt (internal pressure)

▵P (transmembrane pressure)

PArt (arterial pressure)

return obstruction (high PArt, high PInt, stable △P)

management of return obstruction

MAP (only for VA ECMO)

MAP goal in VA ECMO

hypotension in VA ECMO

hypertension in VA ECMO

oxygenation(back to contents)

oxygenation

SvO2 (venous drainage oxygen saturation)

general SvO2 interpretation

causes of low SvO2

management of low SvO2 may include

FdO2 (fraction of delivered O2), aka FsO2 (fraction of sweep gas O2)

VV ECMO

VA ECMO

SarO2 (arterial return saturation) & ParO2 (pO2 in arterial return)

VV ECMO

VA ECMO

causes of low SarO2 & low ParO2

mechanical ventilator settings regarding oxygenation

VV ECMO or central VA ECMO: total lung rest settings

VV ECMO or central VA ECMO: partial lung rest settings with some oxygenation

peripheral VA ECMO (with ejection): native lung oxygenation must always be adequate

SpO2 (patient's oxygenation)

SpO2 goal on VV ECMO

SpO2 goal on VA ECMO

SpO2 goal in pregnancy

related topics

NIRS (near-infrared spectroscopy)

NIRS to evaluate CNS perfusion

NIRS to evaluate limb perfusion

CO2 clearance(back to contents)

CO2 clearance

sweep gas flow rate

sweep flow rate basics

sweep flow in VV ECMO or central VA ECMO

initial sweep flow & pCO2 management

subsequent titration of sweep flow

weaning off VV ECMO

sweep flow in peripheral VA ECMO

mechanical ventilator settings regarding CO2 clearance

VV ECMO, or central VA ECMO

peripheral VA ECMO: conventional ventilation strategy

peripheral VA ECMO: MPCC strategy (Membrane-Predominant CO2 Clearance)

etCO2

VV ECMO

VA ECMO

pCO2 & pH goals

RPM & flow
(back to contents)

intravascular pressures
(back to contents)

evaluation of native cardiac output (CO_native)

P_ven (venous pressure) & drainage insufficiency

causes of excessively negative P_ven (aka drainage insufficiency)

P_Int (internal pressure)

P_Art (arterial pressure)

return obstruction (high P_Art, high P_Int, stable △P)

**MAP (only for VA ECMO)**

oxygenation
(back to contents)

S_vO₂ (venous drainage oxygen saturation)

general S_vO₂ interpretation

causes of low S_vO₂

management of low S_vO₂ may include

F_dO₂ (fraction of delivered O2), aka FsO2 (fraction of sweep gas O2)

S_arO₂ (arterial return saturation) & P_arO₂ (pO2 in arterial return)

S_pO₂(patient's oxygenation)

S_pO₂ goal on VV ECMO

S_pO₂ goal on VA ECMO

S_pO₂ goal in pregnancy

CO2 clearance
(back to contents)

mechanical ventilator settings regarding CO₂ clearance

low circuit flow
(back to contents)

membrane lung dysfunction
(back to contents)

systemic desaturation in VV ECMO
(back to contents)

(#5) consider measures to increase S_vO₂ (especially if S_vO₂ is <60%)

weaning off VV ECMO
(back to contents)

RV dysfunction in VV ECMO
(back to contents)

systemic desaturation in VA ECMO
(back to contents)

LV distension
(back to contents)

differential hypoxemia (aka north-south syndrome)
(back to contents)