Background ECMO is a life support machine replaces the function of - - PDF document

Lesson 19 Extra Corporeal Membrane Oxygenation (ECMO)

Ettore Lanzarone May 13, 2020

MEDICAL SUPPORT SYSTEMS FOR CHRONIC DISEASES

Engineering and Management for Health University of Bergamo

LESSON 19

Background

ECMO is a life support machine replaces the function of the heart and lungs, used for patients with severe and life-threatening illness that stops their heart or lungs from working properly.

• People who need support from an ECMO machine are

cared for in an intensive care unit (ICU).

• Typically, people are supported by an ECMO machine

for only a few hours to days, but may require it for a few weeks.

OXYGNATOR PUMP HEAT EXCHANGER

Lesson 19

Background

ECMO is used to help people whose:

• Lungs cannot provide enough oxygen to the body

even when given extra oxygen

• Lungs cannot get rid of carbon dioxide even with help

from a mechanical ventilator

• Heart cannot pump enough blood to the body

ECMO may also be used to support people with heart or lung disease that cannot be cured while they wait for an

• rgan transplant (e.g., new heart and/or lungs).

OXYGNATOR PUMP HEAT EXCHANGER

Background

The ECMO machine is connected to a patient through plastic tubes (cannula). These tubes are placed in large veins and arteries in the legs, neck or chest. The ECMO machine pumps blood from the patient’s body to an artificial lung (oxygenator) that adds oxygen to it and removes carbon dioxide. Patients on ECMO are also given a medication to thin the blood (e.g., heparin) so it does not clot. Any patient connected to an ECMO machine in the ICU is also connected to monitors. They measure heart rate, blood pressure, oxygen and carbon dioxide levels, and level of heparin.

OXYGNATOR PUMP HEAT EXCHANGER

Lesson 19

Background

Extra corporeal circuits started to appear about in 1950, due to the technical difficulties of the oxygenation function. Example of experiment in dog in 1940

Background

The core of the ECMO machine is the oxygenator. We will focus on dimensioning and controlling the oxygenator. The dimensioning is an off-line procedure (the patient receives a given oxygenator with fixed characteristics), while the control on-line (perfusion conditions can be varied during ECMO). Thus, we will address:

• Dimensioning
• Control

Lesson 19

Oxygenator

The idea is to mimic the lung. They have a modular structure, whose exchange unit is the alveolus, a sort of bag containing the air coming from the bronchi, around which a network of capillaries is wrapped. Mass exchange (oxygenation and CO2 extraction of from blood are regulated by the Fick's law). Its rigorous formulation of this law is differential terms, but dimensioning and control of oxygenators its expression it in finite terms is sufficient:

R p k N

partial

 

p p

1 2

N

Oxygenator

2

min m ml area flow N   

mmHg p partial  

R p k N

partial

 

with:

Gas flow N transferred from the system 1 to the system 2 is directly proportional to the partial pressure difference

• f the same between the two compartments and is

inversely proportional to a flow resistance, which is represented by the obstacle between the two chambers. Systems 1 and 2 may contain gases, liquids or a liquid and a gas, but the law remains unchanged.

Lesson 19

Oxygenator

It is possible to identify an analogy between Fick's law and Ohm's law, with the following correspondences: N (gas flow)  I (electrical current) p (partial pressure difference)  V (potential difference) R (resistance to flow)  R (electrical resistance)

Oxygenator

The blood comes into contact with the alveolar atmosphere through a partition wall, consisting of several biological membranes. In an average adult, the lungs have an exchange surface at the alveolar level of about 50-70 m2. Likely, in oxygenators, the exchange surface can be very resized. 1. The lungs are sized to guarantee the exchange even during the performance of a high physical activity, while oxygenators must guarantee the oxygenation of a patient in the ICU, whose oxygen demand is limited; already for this, the surface can be reduced about 5 times. Notice that, without making intense efforts, even people with only one lung can survive. 2. The composition of the gas that oxygenates the blood is a parameter that can be directly set and controlled, therefore it is possible to use a mixture whose oxygen content is much higher than that

• f the alveolar atmosphere. An increase of p produces an increase in the flow and consequently an

increase in the quantity of oxygen exchanged.

Lesson 19

Oxygenator

The composition of the external air is:

• 20% of O2 (also depending on the altitude)
• 80% of N2
• 0.04% of CO2

During the inspiration phase, the air coming from the external environment is mixed with the “exhaust gases” of metabolic processes, with a different composition. Thus, the average composition of the alveolar air is characterized by intermediate conditions:

• 13% of O2
• 6% of CO2

The amount of N2 remains unchanged as it is not exchanged. These values in the alveolar air correspond to:

• pO2 = 100 mmHg
• pCO2 = 40 mmHg

The relative average partial pressures in the venous blood reaching the lungs are:

• pO2 = 40 mmHg
• pCO2 = 46 mmHg

Oxygenator

Therefore, in the case of oxygen, the pO2 between gas and blood is about 60 mmHg. This corresponds to the required 50-70m2. To reduce the area, a supply of air with higher pO2 can be exploited (up to the pure oxygen with pO2 = 760mmHg, i.e., the atmospheric pressure). Thus, pO2 can be increased up to pO2 = 760 mmHg – 40 mmHg = 720 mmHg. This value is about 10 times greater than the physiological one, so it requires a surface 10 times smaller. An area of about 7 m2 will suffice, which is the size used in several oxygenators.

Lesson 19

Oxygenator

Oxygen and carbon dioxide are transported by blood in two ways:

• Dissolved in plasma
• Linked to hemoglobin (Hb) in red cells

Only the first way would not be enough to guarantee the oxygenation to tissues and this explain the role of Hb in red cells. On average, the amount of Hb in the blood at the physiological Ht = 45% is about 14g per 100 ml and each gram of Hb is able to bind, at its maximum capacity, 1.36 ml of oxygen. In this situation it is said that arterial blood is 100% saturated. Actually, arterial blood is 98-99% saturated.

Oxygenator

Abacus that relates pO2, Sat and concentration of linked O2 (which is about equal to the total amount). These relationships depend on Ht and temperature.

Lesson 19

Oxygenator

Considering these numbers, the exchanged quantities are: With a blood flow of 5 l/min the overall quantities are: The dissolved quantity is negligible and thus neglected.

Oxygenator

Unbalancing is compensated by eliminating H20 in the urine.

Lesson 19

Oxygenator

Now, let us focus on the resistance to flow R. Gases meet a series of resistances as they pass. As for O2:

• the first barrier is the alveolar membrane, a

semipermeable membrane that opposes its passage offering a certain resistance;

• the oxygen molecule passes from the

alveolar membrane to the capillary membrane through the interstitial fluid;

• before reaching the blood, it also crosses

the membrane that constitutes the capillary wall. C02 does the opposite route.

Oxygenator

We start in a disadvantaged situation compared to the lung, at least from the geometric point of view.

• Technology is not yet able to produce membranes as thin and permeable as nature

does.

• It is impossible to build conducts for blood passage with transversal sections of radius
• f 8-10 m (like the capillaries).

By schematizing an oxygenator as a container in which a membrane separates the gas compartment from the blood, we can rewrite Fick's law as (resistances in series):

s s m m partial

D t D t p k N   

tm = thickness of membrane ts = thickness of the blood film Dm = diffusion coefficient of the gas through the membrane Ds = coefficient of diffusion of the gas in the blood Note that the CO2 diffusion coefficient in blood is 6 to 15 times greater than the O2 one.

Lesson 19

Oxygenator

Classification of oxygenators

There exist three types of oxygenators, which are listed in historical order of appearance: 1. bubble oxygenators; 2. film oxygenators; 3. membrane oxygenators: i. real membrane oxygenators (continuous membrane); ii. hybrid oxygenators (microporous membrane). Nowadays, the most used oxygenator is the membrane one and in particular the hybrid one, even if in terms of market percentage the bubbling oxygenators still cover a good slice. They are used because they damage the blood less, even if they are more expensive. They are used also in the ECMO (“M” is for Membrane).

Oxygenator

The design goal is to reduce the flow resistance R:

• Thin membranes to reduce tm
• Reduce the thickness tbof blood film

Two technological solutions allow to keep the thickness tblow:

• tube bundle: a set of ducts (capillaries) in which one of the two phases flows, separated from the
• ther phase that laps the outer surface of the capillaries
• parallel flat plates: blood flows in the space delimited by two plates, while gas flows in the

contiguous interspace between two other plates. With these configurations, the thickness of the blood film is defined as the semi-distance between two membranes.

s s m m partial

D t D t p k N   

Lesson 19

Tube bundle Parallel flat plates

Oxygenator

The principles are the same of the heat exchangers. Pictures refer to exchangers because they are easy to depict.

Oxygenator

It makes sense to talk about a history of the ppartial along the mass exchanger in the Fick's formula, as the partial pressure difference between the gas and blood side vary with the mass exchange. Let us consider a schematized oxygenator consisting of a single tube, inside which the blood flows and licked

• utside by oxygen, perhaps in counter-current (we will

always treat oxygenators in counter-current). The partial pressure difference between the gas and blood is not identical along the tube.

s s m m partial

D t D t p k N   

Lesson 19

Oxygenator

In this case, the ppartial to consider in the Fick’s formula is the so-called mean logarithmic difference. In the counter-current:

              

final initial final initial

ln p p p p ppartial

   

 

   

 

        

             

blood initial 2 gas final 2 blood final 2 gas initial 2 blood initial 2 gas final 2 blood final 2 gas initial 2

ln

O O O O O O O O partial

p p p p p p p p p

Oxygenator

The design goal is to reduce the flow resistance R:

• Increase Dm
• Increase Db

The membrane coefficient Dm depends on the characteristics

• f the membrane and is fixed once the membrane is decided.

The blood coefficients Db depends on flow characteristics; turbulent flow has higher Db than laminar flow, but at the same time to high turbulent flow determines hemolysis.

s s m m partial

D t D t p k N   

Lesson 19

Practical lesson

Dimensioning of an oxygenator; start with O2. 1. Assume a reasonable parameter Db from the literature (approximated with a constant value though it should depend on the working condition you will decide below). 2. Assume Dm = Db/5 and tm = 1 mm. 3. Assume k = 0.9 mol/Pa·m3 [then convert mol into ml based

• n air density equal to 1 kg/m3].

4. Dimension a single capillary, and thus tb. 5. Decide the flow in a capillary in order to have a velocity similar to the mean velocity in aorta (5 l/min in a vessel of 25 mm of diameter). Actually this choice affects Db but we are approximating with a constant value.

s s m m partial

D t D t p k N   

Practical lesson

6. Assume the pressures in the plot; consider 760 mmHg for the air as maximum value, this will allow the on-line control during the working period of the ECMO. 7. Find the adequate N given the pressures. 8. N contains the exchange membrane area of a capillary; based on the already decided size, set the length of the pipeline to get the desired N. 9. Finally, decide the number of capillaries in parallel to have a total of 5 l/min.

s s m m partial

D t D t p k N    Dimensioning of an oxygenator; start with O2.

Lesson 19

Practical lesson

Dimensioning of an oxygenator; now consider CO2. 1. Assume the same Db for both O2 and CO2. 2. Some variables are fixed by the dimensioning of O2. 3. You can only tune the pCO2 in the air to pass from the venous pCO2 to the arterial pCO2.

s s m m partial

D t D t p k N   