Riassunto del corso di Sistemi di Supporto alla Vita

Life support systems

Lez. 1 – 13.03.2015

We will deal with mechanical and metabolic devices.

Mechanical devices

• All those systems used to assist circulation (mainly made up by pumps), like:
• LVAD (Left Ventricular Assist Device)
• ECMO, that is an assistance to the circulation which is run on the blind side of the patient; it is also a sort of oxygenation assistance
• IABP (Intra-Aortic Balloon Pump), another system for oxygenation assistance
• TAH (Total Artificial Heart), which doesn’t exist yet on the market

Metabolic devices

• Pancreas pancreatic support
• Respiration-assisted ventilation respiratory support
• Renal support or assistance

Respiratory support and the so-called artificial pancreas are the only two systems that are not necessarily involving blood in the action of the system; all the others will involve blood. In fact, respiration can be run also by the airside, not only by the blood side.

All devices will be treated under different aspects that are the duration of implantation, the site of implantation (which means invasiveness, like 'how invasive?'); of course, there is a relationship between the duration of an implantation and its invasiveness. Actually, we have different kinds of implantation, with devices that could be:

• Paracorporeal for short – medium duration
• Extracorporeal for short duration and/or repeatable (e.g., dialysis)
• Intracorporeal (totally implantable) for long duration, when transplantation is not an option for the patient (e.g., artificial ventricles). In this case, the implantation should be as invasive as possible in order to avoid any risk of infection.

Which kind of machines do we have to use? If we deal with air, we can use compressors (they are just actuators), but if we deal with blood we can use pumps, which can be:

• Continuous
• Pulsatile or intermittent

The most common energy source is electric energy. We can supply it to both pumps and compressors, and we can use batteries (even if they have a short life) in order to make the patient be sufficiently not dependent on the site where energy is produced. We might have different levels of implantation and we can put some more durable devices inside the body and, then, have just a subcutaneous implantation, like batteries (that need to be recharged more frequently). This is what's done with pacemakers.

The problem of being rechargeable is big (also because battery duration decreases over time): we need a source that allows the patient to always have energy!

Moreover, we have to choose the material. The site of implantation influences the choice, too: if we are dealing with an intracorporeal device, we can’t choose a material that loses performance very rapidly because this would mean we have to open the patient again to substitute it. If we are dealing with extracorporeal devices, we are allowed to choose materials that are biocompatible, not toxic, but poor materials, which means that they will last for a short time, because we can change the device in case of emergency. If you have a valve prosthesis implanted, you can’t choose a bad material with low durability. You need to choose a material whose duration is assessed for longer and longer time than the one of the application duration. But if this valve is implanted and is put on a device that is placed extracorporeal to the patient, the problem is less heavy because, in any case, you can think to substitute that valve. Also, the costs are related: the smarter the material, the higher the related cost.

Cardiomyoplasty

It’s a therapy for cardiac patients. The technique consists of different phases:

• Cut off the dorsal muscles
• Train these muscles in order to make them switch to a muscle that is capable of undergoing heavy work without producing lactic acid
• Take this muscle and reverse it towards the anterior part of the body
• Wrap the heart into these muscles
• Stimulate these muscles so that they can perform contraction and relaxation and so can assist the heart

It’s a good technique, but the patient becomes hunchbacked since he hasn’t the dorsal muscles anymore, so his social recovery could be a problem. Actually, social recovery is very important, and that’s the reason why all the people that deal with artificial hands are trying to develop very intelligent hands that can be moved by neural controls, without leaving them as steel or other materials, but covered by a material that resembles skin. Moreover, they are trying to give a tactile sensation for those who touch them that is similar to the one you would have by touching real skin.

Mechanical assistance

The simplest mechanical assistance is the Intra-Aortic Balloon Pump, which is used to make the heart recover especially after infarction.

Intra-Aortic Balloon Pump

A patient, who has undergone infarction, has been brought to the I.C.U. (Intensive Care Unit) and is put on the so-called counterpulsation. Actually, the heart is beating and it’s infarcted. The main goals of this therapy are:

• Reduce the work of the heart
• Increase coronary perfusion

How can you do this? Consider the left ventricle and the aorta, with the three branches. We have to insert through the femoral artery a catheter, which is connected to a compressor, and come up the descending aorta. This catheter has a peculiarity: on its tip, it has a balloon that is empty at the beginning. If the compressor works (intermittently), the balloon would inflate and then, when the vacuum pump is activated, the balloon deflates. So, the balloon may inflate or deflate, depending on the kind of machine connected to the balloon.

Why counterpulsation? Because the balloon inflates when the ventricle is in the diastolic phase and deflates when the ventricle is in systolic phase. This is a quite invasive procedure: it’s a sort of extracorporeal procedure because the machine is outside the body and not in the body, even if you have a catheter that comes inside. Therefore, the material of this kind of device has to be biocompatible, but also sufficiently smooth and flexible. At the same time, it must have a sort of rigidity otherwise it wouldn’t be able to come up the artery. The balloon normally is made of silicone and here comes a problem because silicone is a material that normally can be patched and glued only to silicone. It is not responding to any other material and is not capable of being glued to other materials; so, the catheter should be made of silicone but it’s also too expensive and for these reasons, it’s usually made of PVC. In order to connect silicone to the other material, you can use the so-called crown infect, a procedure that is obtained by charging the materials properly: you work on the material and you treat the surface of the material so to make silicone able to be glued to the other material, also by electric treatment of the surfaces. Actually, you can expose the charging of the materials and, since they are charged differently on the side of the connection, they can be compatible: by treating the material, you change its attitude to be glued. In this way, you obtain a ceiling of the structures that is really stable.

How to make this system work? Which kind of gas should be used? No physiological solution is used because of the inertia: if you used a liquid, the inertial effect would be very high. The catheter is very small in diameter and you would have also high-pressure drops so it would be quite complicated to manage the behavior of the catheter and the balloon, too. Moreover, you mustn’t have any air in blood otherwise you would embolize blood so for sure you don’t use air. You use a gas: at the beginning, Helium was used, but also He could create emboli so it was abolished. Since it’s a mechanical device, that you put inside, you must be sure that in case of rupture of the balloon, you don’t put the patient at risk so you must use a very soluble and biocompatible gas in blood. The most soluble gas is CO₂ so normally it is used due to its high solubility in blood.

Design principles: you need to choose a soluble gas, then you look for the most biocompatible soluble gasses and so you choose CO₂. The design principle is: “I want a gas which is sufficiently/highly soluble in blood” because I need the solubility to avoid any risk in case of rupture.

How do you design? / Which are the design principles of a device? The answer is not how the device works, but which are the principles the device is based on and that can be applied to any device of the same kind.

How can we obtain the correct counterpulsation? What do I need to make the system work properly? We may need to know where we are with the tip of the catheter. More importantly, since the heart is pathological, we need synchronization with the beat in our heart: the counterpulsation has to be triggered. We have to put a sort of pacemaker in order to give the heart the right rhythm. We need the heart to beat at a fixed rate otherwise the therapy will be absolutely not constant (after infarction the heart is fibrillating, is moving with different frequencies, is changing frequency randomly and so on). I need the system that not only triggers the contraction of the heart but allows a normal and stabilized activity because I need the heart to work at a stable pulsation, so at a fixed rate. It is quite impossible to put a pacemaker on a patient on an ambulance: this is a typical therapy that has to be put on in the hospital, in I.C.U.

You need to know perfectly when systole and diastole occur otherwise you risk inflating or deflating the balloon not synchronously with the heart rate. If you inflate the balloon when the heart is in systole, you will cause another infarction, or if you deflate the balloon when the heart is in diastole, you will have no effects.

We want to reach the two goals. We start with the second one:

1. How can you increase coronary perfusion? Which are the determinants of coronary perfusion? Coronary perfusion is created by coronary flow rate, ΔP = ΔP / R where ΔP = pressure gradient across coronary circulation R = hydraulic resistance exerted by coronary circulation (it’s the same; when the balloon is inflated, there are no external resistance factors affecting the system).

The coronary circulation takes origin from the aortic root and ends in the right atrium so: ΔP = P_ao - P_ra where P_ao = aortic pressure and P_ra = right atrium pressure.

So, in order to increase coronary perfusion, we have to increase the aortic pressure, P_ao, assuming ΔP ≈ P_ao. We may have also some stenosis on the coronaries so we will need to increase P_ao much more to win the stenotic resistance.

In diastole coronaries are open, for two reasons: one is the reason of the heart so coronary fills very well when the heart is in diastole and the other one is that the coronary ostium is open because the valve is closed and so the leaflets on the aortic valve don’t close the entrance of the coronary. So, when the heart is in diastole, the aortic valve is closed, and the balloon is inflated. This inflation makes this portion of the aorta be pressurized and so coronary perfusion will increase.

The balloon deflates synchronously to the opening of the valve.

2. How can you reduce the work of the heart? The heart is a pump, a mechanical device, whose work is given by W = P_lv · ΔV where P_lv = intraventricular pressure during systole. To decrease W, we can decrease P_lv. During systole, you get an increasing pressure in the ventricle because it is contracting. Also, the valve is open and the ventricle forms a sort of continuous tube with the aorta, so you have ejection. As soon as the aortic valve opens, the balloon is deflated, obtaining a reduced P_lv. Why? Because you create a sort of suction (it is not a problem regarding volume or resistance because the heart didn’t feel any resistance because the valve was closed). When you open the valve, the balloon is deflated and you have a suction because there is a dynamic effect because you have this volume that becomes free for the passage instantaneously. This is not sufficient to reduce W because if you reduce the afterload (P_ao), you will increase the flow rate pumped by the ventricle, not necessarily reducing the work. So why does W decrease when you reduce P_ao? Where is the link between the two reductions? Because we have a pacemaker on this heart so the flow rate pumped by the heart is given by Q = f · SV where f = frequency, it is constant because of the pacemaker SV = stroke volume, it is constant because the ventricle doesn’t change its volume.

So, actually, you are working with a constant (or almost constant) flow rate: if you reduce the afterload, you get a reduced preload (P_ra), it’s again a matter of ΔP.

In this case: ΔP = P_ao - P_ra = Q · R.

This means that if P_ao decreases, also P_ra decreases. In normal conditions, if P_ra decreases, P_ao increases but in this case, it doesn’t because we have a pacemaker, which maintains the flow rate constant.

This kind of therapy can be used and the patient can be under counterpulsation for a short time, maximum 15 days because if the patient doesn’t respond to this kind of therapy, it means that you have to use other systems. If the heart doesn’t recover properly in these 15 days, it means that the patient needs to be put on cardiac assistance with mechanical devices, more invasive and much more powerful. In fact, counterpulsation just allows the recovery of the heart, while other mechanical systems would help and assist the heart during pumping.

Moreover, you can’t maintain the balloon in position for many days because you have to remember that the heart is pumping so you have a flow rate with a high velocity in these portions, which can cause the movement and the fluctuation of the balloon inside the aorta when the catheter has the balloon deflated. These fluctuations may cause also hurting of the intima of the aorta because of the collisions between the catheter and the internal part of the vessel and it could cause also some clot growing and so a disease affecting the aorta. Therefore, you can treat the patient a couple of weeks, no more. In these situations, you have also to give drugs to the patient because of the necessity to make the heart recover completely.

Lez. 2 – 20.03.2015

Ventricular Assist Devices (V.A.D.)

V.A.D. are those systems that may assist the heart function for a long duration. It can be life-long duration or just days, depending on the condition of the patient, on how easily you can find a donor heart and depending on the kind of heart of the patient. When you have to implant a valve in a patient, you implant it because the patient doesn’t respond to any drug therapy or any counterpulsation therapy so he needs to be assisted in heart function, otherwise, he would die. So, there is no possibility of recovery of the native heart. Therefore, we need to know whether the patient will be transplanted or whether this will be a so-called destination-therapy, which is a life-long duration therapy.

How can we know this? We can know it depending on the dimensions of the patient (if he has normal dimensions, it would be quite easy to find a heart). It will also depend on the immunological system of the patient that will guarantee the acceptability of a donated heart by the patient. Therefore, you will have to analyze a sort of possible acceptability of any kind of heart that however has to respond to some criteria, depending on the kind of RH factor, blood group, and other related items. The surgeons of the hospital may know already whether the patient will be potentially implanted or not, or if the patient will never be transplanted.

Either you have a long implantation or a short one, you can’t have many different systems to deal with. You may choose the kind of system in terms of its invasivity and its level of implantability: if you already know that in a few days the patient would be transplanted, it’s quite useless to use a sophisticated system to assist the patient. So, you may need just an extracorporeal support because this kind of assistance would be taken off very quickly. Vice versa, if you think that the heart will be quite difficult to be found (or you are choosing for the patient a life-long implantation), then you better choose a total implantable device so that you can discharge the patient at home. Moreover, the patient is less prone to possible infections that become aggressive and that can enter the body by all the possible connections between the system we have implanted and the outside energy supplied. Also, the level and the positioning of the energy supply is something that has to be chosen or designed by biomedical engineers in terms of different durability of this supply. We can have short/life energy supply or short/life duration but we need to have very long-lasting energy supply.

We already said that the battery is probably not the best option to feed the system; this is why, when you deal with a total artificial project, you will concentrate some nuclear power to be used to give energy to the system because nuclear power is long-lasting, is small and so can be put inside the body. When the patient wearing the nuclear battery will die by natural death, you will have to treat that patient as radioactive waste: you can’t bury an individual who is wearing a nuclear battery otherwise it would be hazardous for the environment and for the people and you can’t cremate it because it would explode.

The different kinds of energy source and the different level of invasivity depend on the duration we foresee for the specific treatment.