Control of breathing by ECMO in ARDS

Tommaso Mauri

University of Milan – ItalyPlug working group – ESICM

I have nothing to disclose.

Within the last 12 months I have not had any type of financial arrangement or affiliation with commercial interests related to the

content of this continuing education activity that requires disclosure.

DISCLOSURE

Control of breathing in ARDS

63 yo, severe ARDS, ECMO day 13, SURVIVED

If ECMO is able to maintain normal PaCO2 and PaO2, then ventilation is no more needed

Nunn’s Applied Resp Phys 2010

Control of breathing during ECMO

ECMO

ECMO can replace ventilation

• Five anesthetized and paralyzed healthy lambs

• NO ventilation (PEEP 5) + AV ECMO for 24 hours

Kolobow T et al. J Thor Cardiovasc Surg 1978

ECMO and spontaneous ventilation?

Seven healthy lambs

Awake, spont. breathing

AV ECMO

Increasing gas flow to increase VCO2 ML

Control of ventilation by ECMO

Linear decrease of minute ventilation at increased VCO2-ML

At 90-100% of VCO2

removed, ventilation decreased to 5-20% of the baseline (no ECMO)

Kolobow T et al. Anesthesiology 1977

ECMO VCO2 / total VCO2

0 20 40 60 80 100

Red

uctio

nin

Min

ute

Ve

ntila

tio

n

[% o

f C

ontr

ol]

0

20

40

60

80

100r

2=0.74

p<0.001slope=0.94y0= -3.6

Langer T Crit Care Med 2014

Control of breathing by ECMO

Healthy non-sedated spontaneously breathing sheep.

vvECMO.

Linear reduction of minute ventilation down to <20%.

ECMO-induced apnea in healthy lungs

Canet E, J Appl Physiol 1993

ECMO-induced apnea at different levels of hypoxemia

Apnea thresholds: PaCO2 has to be lower to induce apnea in the presence of hypoxemia

Physiologic control of breathing

Vaporidi K. et al. Am J Respir Crit Care Med 2019

Minute ventilation is the intersection between the:metabolic hyperbola and the PaCO2-MVe curve

Sleep

Min

ute

ven

tila

tio

n

PaCO2

GF low

GF intermediate

GF high

ECMO shifts the metabolic hyperbola

ECMO can control minute ventilation by shifting down the metabolic hyperbola through decreased VCO2 of the pt

↓VCO2-ECMO↑ VCO2-NL

↑VCO2-ECMO↓ VCO2-NL

Interim conclusions

Experimental studies show that in healthy animals increased elimination of CO2 by ECMO can decrease minute ventilation down to apnea

But..

Is ARDS equal to health?

= ???

Respiratory drive in ARDS

First difference:

In ARDS, respiratory drive is increased by multiple derangements of physiology that determine exaggerated response to changes in PaCO2

Even in the presence of low PaCO2 values, drive might remain elevated

Spinelli E. et al. Respiratory drive in the acute respiratory distress syndrome: pathophysiology, monitoring and clinical targets. Submitted.

IN ARDS

Second difference: in ARDS, the PaCO2-MVe curve separates from the central brain curve because of sedation, diaphragm weakness and increased lung elastance

Even in the presence of increased drive, minute ventilation could remain low

Vaporidi K. et al. Am J Respir Crit Care Med 2019

Minute ventilation in ARDS

On the one hand, control of minute ventilation could be ineffective because of increased drive

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On the other, control could be effective because ventilation is far lower than the level desired by brain centers

ECMO and control of breathing in ARDS

Control of breathing during recovery from ARDS

Marcolin R Trans Am Soc Artif Inter Organs 1986

Six patients recovering from severe ARF, ECMO could reduce minute ventilation to almost zero

Mean 0.22 36

Modifying VCO2 by ECMO

Mauri T et al. Anesthesiology 2016

Resting GF GF 050% 25%

VCO2 NL

4.4±1.2 l/min

ECMO can modulate patient’s VCO2 by changing the VCO2 of the membrane lung

Eight patients recovering from severe ARDS, enrolled after the clinical team switched them to PSV

Decreasing ECMO support during PSV and NAVA

Mauri T Anesthesiology 2016

Control of respiratory drive and effort

At resting, 100% GF:

Two patients with Eadi 10-15

One pt with P0.1 >2

No pts with RR >30Two pts with RR >20

One pt with Pmus >10

Mauri T Anesthesiology 2016

Control of transpulmonary pressure

Mauri T Anesthesiology 2016

0 20 40 60 80 100

0

20

40

60

80

100r

2=0.59

p<0.001

slope=1.1

y0= -24.0

Reduction in M

inute

Ventila

tion

[% o

f C

ontr

ol]

ECMO VCO2 / total VCO2

Langer T Crit Care Med 2014

Control of breathing in early severe ARDS

Early severe ARDS in non-sedated spontaneously breathing sheep

VCO2 almost completely removed by ECMO but small reduction of spont MV

Control of spontaneous breathing in early severe ARDS – clinical series 1

• 6 severe ARDS pts treated by awake ECMO to avoid intubation

• 50% successfully treated to recovery without intubation

• Reasons for intubation: PNX, accidental removal of ECMO and CA, exhaustion. Two (66%) died after intubation.

Hoeper et al. Int Care Med 2013

30 consecutive ARDS pts on controlled ventilation and ECMO

Stop sedation and paralysis within 5-7 days form ECMO start

Extubated if:

• RASS -1 to +1

• Adequate airway protection

• Able to cough

• Fever controlled

• No alveolar plasma leak

• Hemodynamic stability

• No major bleeding

Crotti et al. Anesthesiology 2017

Control of spontaneous breathing in early severe ARDS – clinical series 2

Awake ECMO in Milan: 50% success

Crotti et al. Anesthesiology 2017

ARDS SB-ECMO

re-intubated4/8 (50%)

Crotti et al. Anesthesiology 2017

Characteristics of ARDS that allow SB

Factors associated with impossibility to perform a spontaneous breathing test: p/f, days of ventilation, SOFA, lung weight.

Mauri T Int Care Med 2016

Sometimes, ECMO can’t control ventilation

ECMO day 7, Crs 15 ml/cmH2O, lack of control of respiratory drive by ECMO

What are the risk factors correlated with poor control of respiratory drive?

Control of breathing in early ARDS

15 subjects with severe ARDS on ECMO since 1-7 days

Sedation decreased to obtain RASS -2 to 0, presence of inspiratory trigger, PSV 5-10 cmH2O, clinical PEEP (15 [12-18] cmH2O)

PaCO2, pH and PaO2 within physiologic ranges

ECMO GF increased to obtain VCO2-ECMO/tot >90%:

• Apnea in 3 subjects

• Normal breathing pattern in 6 (RSBI ≤105 bpm/l)

• Rapid shallow breathing in 6 (RSBI >105 bpm/l)

Spinelli E. et al. Spontaneous breathing patterns during maximal extra-corporeal CO2 removal in subjects with early severe ARDS. Respir Care, in press

Worse control correlates with severity and outcome?

Hospital mortality within the study population was 0/3 vs. 0/6 vs. 3/6 (apnea vs. RSBI ≤105 bpm/l vs. RSBI >105 bpm/l; p = 0.169)

Spinelli E. et al. Spontaneous breathing patterns during maximal extra-corporeal CO2 removal in subjects with early severe ARDS. Respir Care, in press

Conclusions

• In healthy animals and in patients recovering from severe ARDS, ECMO can control spontaneousbreathing

• In early severe ARDS large variability exists and ECMO can’t control breathing in a subgroup of patients

• These might be the most severe one