EP2344219A1 - Anesthésique gazeux à base de xénon destiné à être administré par le biais d'un c ur-poumon artificiel - Google Patents

Anesthésique gazeux à base de xénon destiné à être administré par le biais d'un c ur-poumon artificiel

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Publication number
EP2344219A1
EP2344219A1 EP09783487A EP09783487A EP2344219A1 EP 2344219 A1 EP2344219 A1 EP 2344219A1 EP 09783487 A EP09783487 A EP 09783487A EP 09783487 A EP09783487 A EP 09783487A EP 2344219 A1 EP2344219 A1 EP 2344219A1
Authority
EP
European Patent Office
Prior art keywords
xenon
membrane
blood
patient
heart
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP09783487A
Other languages
German (de)
English (en)
Inventor
Thomas Marx
Gabriela Apiou
Reginald Birngruber
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Air Liquide SA
LAir Liquide SA pour lEtude et lExploitation des Procedes Georges Claude
Original Assignee
Air Liquide SA
LAir Liquide SA pour lEtude et lExploitation des Procedes Georges Claude
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Air Liquide SA, LAir Liquide SA pour lEtude et lExploitation des Procedes Georges Claude filed Critical Air Liquide SA
Publication of EP2344219A1 publication Critical patent/EP2344219A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
    • A61M1/1698—Blood oxygenators with or without heat-exchangers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/02—Gases
    • A61M2202/0291—Xenon

Definitions

  • the present invention relates to a method and an apparatus for providing anaesthesia to a patient undergoing cardiopulmonary bypass (CPB).
  • CPB cardiopulmonary bypass
  • Some surgical procedures require the temporary cessation of the normal activity of the heart and/or lungs of a patient, e.g., lung surgery, aortic repair surgery, cardiac surgery.
  • oxygenation of the blood and the removal of carbon dioxide from the blood are achieved using extracorporeal oxygenators, such as bubble oxygenators, hollow fibre membranes, membrane plates or the like, and a blood pumping system.
  • extracorporeal oxygenators such as bubble oxygenators, hollow fibre membranes, membrane plates or the like
  • a blood pumping system a blood pumping system.
  • Devices combining an oxygenator and pumping system are known as cardiopulmonary bypass (CPB) systems or by the more common name, heart-lung machines.
  • CPB cardiopulmonary bypass
  • CPB systems are also used in the case of severe lung failure, such as ECMO or extracorporeal membrane oxygenation, with or without insufficiency of the cardiac system.
  • Patients undergoing cardiopulmonary bypass should be anaesthetized in order to render them insensitive to pain during the medical intervention.
  • anaesthesia is administered before, during and after the CPB phase by intravenous administration of one or more pain-reducing substances in combination with sleep inducing hypnotic agents. This can also be achieved by administering to the patients volatile anaesthetics by inhalation, as in classical anaesthesia.
  • the agents or substances used during CPB to achieve anaesthesia can have severe side effects, impair organ function, cause intra- and postoperative complications and increase mortality.
  • the most severe damage observed with the use of such agents or substances involves impairment of the pumping function of the heart and a decrease in blood pressure, which can subsequently lead to organ hypo-perfusion.
  • organ hypoperfusion can lead to the general dysfunction of a variety of organs, which may cause irreversible damage to the body.
  • intravenous anaesthetic agents are normally metabolized in the liver.
  • IV agents intravenous anaesthetic agents
  • limited capacity of the rate of metabolism in the liver results in various problems associated with the administering of such IV agents, including an unpredictable prolonging of the IV agent's effects in the patients, in adverse side effects for the patient and, in some cases, in fatal over-dosages.
  • volatile anaesthetic agents are not ideal since they also have drawbacks, in particular, nausea, a decrease in heart function and a reduction of blood pressure.
  • the CPB is rapid change of the blood temperature that usually happens during a CPB procedure.
  • the blood temperature during CPB ranges from about 16° C (corresponding to the deep hypothermia period during which the temporary total arrest of cardiac function occurs) to about 40 0 C (corresponding to the re-warming/re-perfusion period that follows the deep hypothermia period).
  • the vapour pressures of volatile agents differs from between about 500% to about 700%, leading therefore, from time to time, as compared to the normal blood temperature of 37.6 0 C, to severe over-dosages, possible toxicity and/or adverse side effects, or to the contrary, under-dosages, and in certain cases possible intra-operative awareness of the patient and recall.
  • halogenated fluorocarbons can react with one or more plastic components of the CPB system thereby leading to dysfunction or inoperability of the oxygenation membranes and/or the dissolving of lubricants used in the pumps, and consequently the impairment of the function of the CPB system.
  • the Table below illustrates the degree of compatibility of trichlorofluoromethane with some known plastics.
  • xenon gas as an anaesthetic agent during CPB operations. See e.g., G. Lockwood et al, Feasibility and safety of delivering xenon to patients undergoing coronary artery bypass graft surgery while on cardiopulmonary bypass: phase I study ; Anesthesiology 2006; 104: pp.458-65.
  • xenon is a good candidate for providing anaesthesia during a CPB operation as it does not react with oil, plastics and rubbers and, furthermore, does not have a vapour pressure that is highly influenced by rapid changes of the blood temperature of the patient.
  • xenon preserves patient blood pressures within normal ranges not only before and after CPB, but also during the CPB phase, when the blood is circulating through the CPB machine.
  • xenon is also able to limit the negative side effects of a CPB on the pump function of the heart and on the blood pressure of the patient, and their consequences, such as organ mal perfusion and postoperative dysfunctions.
  • a CPB negative side effects of a CPB
  • xenon is also able to limit the negative side effects of a CPB on the pump function of the heart and on the blood pressure of the patient, and their consequences, such as organ mal perfusion and postoperative dysfunctions.
  • Publication No. 2005/238726 discloses methods of controlling neurological deficits in patients who have undergone cardiopulmonary bypass (CPB), wherein xenon is administered prior to the commencement, during and after the CPB phase and when blood is extracted from the body.
  • CPB cardiopulmonary bypass
  • oxygen/xenon is administered by perfusion using a specialized heart-lung machine into the patient undergoing the CPB procedure along with the removal of carbon dioxide.
  • xenon can be co- administrated with other anaesthetic agents during CPB.
  • co-administrating xenon is advantageous since doing so requires lower doses of anaesthetic compounds, i.e. volatile and/or injectable anaesthetic agents that have to be co-administered with the anaesthetic agent, especially during the CPB phase, but preferably also before and after the CPB phase.
  • a membrane system is commonly used. More precisely, a continuous flow of a gas mixture containing xenon and oxygen is contacted with the gas side of the membrane included in such a membrane system (such as a hollow-fibre membrane) whereas the patient's blood is, more or less at the same time, contacted with the other side of the membrane, i.e. the "blood side", thereby resulting in gas exchanges through the membrane between the gas side and the blood side of the membrane.
  • a membrane system such as a hollow-fibre membrane
  • the waste gases are not reintroduced into the membrane system but are instead vented and lost in the ambient air, i.e., in the operation room.
  • the rate of diffusion of xenon coming from the blood through the membrane is too rapid, i.e. occurs at a higher than intended rate, then the level of anaesthesia administered to the patient may not be sufficient since the amount of xenon dissolved in the patient's blood would be too low, which in turn could lead to possible intra-operative awareness of the patient and recall. This of course is not acceptable.
  • the first problem to be solved requires a device and a method for obtaining an efficient anaesthesia for a patient undergoing CPB, wherein xenon gas is used as a anaesthetic agent, alone or in combination with any other anaesthetic substance or compound, which overcomes, at least partially, all or some the above problems and/or drawbacks.
  • the second problem to be solved requires a device and a method for minimizing losses and consumption of xenon during the anaesthesia of a patient undergoing CPB using xenon as an anaesthetic agent.
  • the third problem to be solved requires a device and a method for maintaining an efficient anaesthesia of a patient undergoing CPB using xenon as an anaesthetic agent, even during the CPB phase when the blood of the patient is bypassed and travels trough the heart-lung machine.
  • the fourth problem to be solved requires a device and a method for limiting the diffusion through the membrane of the heart-lung machine used during CPB, of xenon dissolved in the blood of a patient towards the gas side of the membrane.
  • One embodiment of the present invention comprises an apparatus for maintaining or providing an anesthesia to a patient undergoing a CPB procedure, comprising :
  • a heart-lung machine comprising at least one membrane having a liquid side and a gas side, and further comprising blood circulating means for circulating blood extracted from the patient and containing a first partial pressure (pXel) of xenon, at least through the heart-lung machine and contacting it with the liquid side of the membrane, - a source of xenon-containing gas in fluid communication with the gas side of the membrane of the heart-lung machine, and
  • pXel first partial pressure
  • - partial pressure controlling means for applying or maintaining a second partial pressure (pXe2) of xenon on the gas side of the membrane such that : pXe2 > 0.5 x pXel.
  • the apparatus of the present invention can comprise one or several of the following features:
  • the membrane is a hollow fiber-type membrane with the gas side of the membrane comprising the internal or external part of the fibers.
  • the source of xenon-containing gas comprises xenon and oxygen, preferably contains at least vol. 20% of oxygen.
  • the membrane is a selective membrane that exhibits a greater coefficient of permeability for O 2 than for xenon, preferably it exhibits a greater coefficient of permeability for CO 2 and O 2 than for xenon.
  • the selective membrane is a nanocarbone-type membrane.
  • Another embodiment of the present invention comprises xenon-containing gas for use in a method for maintaining or providing an anesthesia to a patient undergoing a CPB procedure, comprising the steps described below.
  • said xenon-containing gas comprises xenon and oxygen, preferably at least 20 vol. % of oxygen.
  • the present invention comprises a method for maintaining or providing anesthesia to a patient undergoing an operation in which CPB is used.
  • the steps of the method include: extracting at least a part or portion of the patient's blood from the patient's body, wherein the extracted blood contains a first partial pressure (pXel) of xenon; circulating the extracted blood through a heart-lung machine comprising at least one membrane having a liquid side and a gas side; contacting a xenon-containing gas with the gas side of the at least one membrane of the heart-lung machine and further contacting the patient's blood that is circulating through the heart-lung machine with the liquid side of the at least one membrane; applying or maintaining a second partial pressure (pXe2) of xenon on the gas side of the at least one membrane such that : pXe2 > 0.5 x pXel; and then after the patient's blood has been circulated through the heart-lung machine, re-introducing the xenon-containing blood coming from the heart
  • xenon is also administered to the patient by inhalation of an effective amount of gaseous xenon (in the form of a xenon-containing gas) prior to the commencement of the CPB procedure, e.g., when the anesthesia is induced in the patient and the blood has not yet been extracted from the patient's body.
  • gaseous xenon in the form of a xenon-containing gas
  • the method of the present invention can include one or several of the following features :
  • xenon and oxygen preferably it comprises xenon and at least 20 vol. % of oxygen.
  • - pXe2 > 0.8 x pXel, preferably pXe2 > 0.9 x pXel.
  • the second partial pressure of xenon (pXe2) applied or maintained on the gas side of the membrane is greater than or equal to (pXe2 ⁇ pXel) the first partial pressure of xenon
  • the second partial pressure (pXe2) of xenon applied or maintained on the gas side of the membrane is obtained by adjusting or controlling the amount of xenon in the xenon-containing gas contacted with the gas side of the membrane.
  • the membrane is a hollow fiber-type membrane with the gas side of the membrane comprising the internal or external part of the fibers.
  • the xenon-containing gas contacted with the gas side of the membrane comprises xenon and oxygen, preferably contains at least vol. 20% of oxygen.
  • the xenon-containing gas is obtained by mixing xenon and oxygen inside the heart- lung machine or the xenon-containing gas is obtained by mixing xenon and oxygen prior to introducing the gas into the heart-lung machine.
  • said first partial pressure (pXel) of xenon in the patient's blood is achieved by administering gaseous xenon to the patient by inhalation, preferably said gaseous xenon is in the form of a xenon-containing gas comprising xenon and at least oxygen.
  • gaseous xenon is mixed with at least gaseous oxygen, the proportion of gaseous xenon in the gas mixture being from between 5 and 75% in volume.
  • the method for maintaining or for providing an anesthesia to a patient undergoing a CPB operation comprises the steps of : i) administering to a patient prior to commencement of the CPB operation a first xenon-containing gas, thereby dissolving some xenon in the blood of the patient, ii) starting the CPB by extracting at least a portion of the patient's blood from the patient's body, said extracted blood containing dissolved xenon and CO 2 , iii) circulating the extracted blood through a heart-lung machine comprising at least a membrane having a liquid side and a gas side, said membrane being a selective membrane that exhibits a greater coefficient of permeability for CO 2 and O 2 than for xenon, iv) contacting a second xenon-containing gas and an oxygen-containing gas with the gas side of the membrane of the heart-lung machine and contacting the patient's blood circulating through the heart-lung machine, with the liquid side of the membrane, thereby introducing oxygen
  • the amount of gaseous xenon contained in the first xenon-containing gas is from between about 5 and 75 vol. %.
  • the additional anaesthetic agent is at least a volatile compound to be inhaled by the patient, said volatile compound selected from sevoflurane, desflurane, isoflurane, enflurane and mixtures thereof.
  • the amount of said volatile compound to be inhaled by the patient is from about between 0.05 vol.% and 15 vol. %.
  • the additional anesthetic agent is one or more injectable compounds selected from opiods, hypnotic acting agents, benzodiazepines, barbiturates and mixtures thereof.
  • the first, second or third xenon-containing gas further contains from about between 20 and 90 vol. % of oxygen. - during the CPB operation, the patient is put into hypothermia.
  • the selective membrane is a nanocarbone-type membrane.
  • the method for maintaining or providing an anesthesia to a patient undergoing a CPB procedure comprising the steps of : a) extracting at least a part of the patient's blood from the patient's body, said blood containing a first partial pressure (pXel) of xenon, b) circulating the extracted blood through a heart-lung machine comprising two separate membranes each having a liquid side and a gas side, one membrane for allowing the diffusion of xenon into blood and the other membrane for allowing the diffusion of oxygen into the blood and CO 2 out of the blood, c) either contacting a xenon gas with the gas side of the membrane of the heart lung machine that allows for the diffusion of xenon into the blood, while at the same time contacting the patient's blood circulating through the heart-lung machine with the liquid side of the membrane followed by contacting an oxygen gas with the gas side of the membrane of the heart lung machine that allows for the diffusion of oxygen into the blood and CO 2 out of the blood or contacting an oxygen gas
  • Figure 1 provides a curve showing the vapour pressure of bromochlorodifluoro- methane between -50 0 C and +150 0 C.
  • Figure 2 provides a curve showing the vapour pressure of gaseous xenon (Xe) between -117°C and +20 0 C.
  • Figure 3 illustrates the main steps of a CPB procedure.
  • Xenon is an inert gas that has been used for years as an anaesthetic agent that is inhaled by the patient, i.e. the administering of xenon is normally done via the lungs.
  • it is proposed to administer xenon, during the CPB phase, directly into the blood of the patient by means of a heart-lung machine that is equipped with a gas-exchange membrane.
  • Xenon is a commercially available gas that can be purchased from a gas supplier, such as Air Liquide Sante.
  • the problems discussed in the background can be solved, depending on the embodiment, by either maintaining an adequate xenon partial pressure difference between the gas and blood sides of the one or more membranes utilized, or by using one or more selective membranes, or a combination of both.
  • the present invention provides for a way of maintaining or providing an anesthesia to a patient undergoing a CPB procedure. According to the invention, at least a portion of the patient's blood is extracted from the patient's body, the blood having a first partial pressure (pXel) of xenon.
  • the heart-lung machine As the blood is extracted from the patient's blood, standard means are used for injecting the patient's blood into and circulating it through the heart-lung machine that includes at least one membrane that has a liquid side and a gas side. As the blood is circulated through the machine, it is allowed to come in contact with the liquid side of the one or more such membranes. A xenon-containing gas is contacted with the gas side of the at least one membrane of the heart-lung machine at the same time that the patient's blood that is circulating through the heart-lung machine is contacted with the liquid side of the at least one membrane.
  • the second partial pressure (pXe2) of xenon applied or maintained on the gas side of the at least one membrane is obtained by adjusting or controlling the amount of xenon in the gas mixture (xenon-containing gas) contacted with the gas side of the at least one membrane.
  • a second partial pressure of xenon (pXe2) is applied and/or maintained, using partial pressure controlling means, on the gas side of the at least one membrane such that: pXe2 > 0.5 x pXel (the second partial pressure of xenon is greater than or equal to 0.5 times the first partial pressure of xenon), preferably pXe2 > 0.8 x pXel, even more preferably pXe2 > 0.9 x pXel.
  • Partial pressure controlling means are or comprise any device or system that is able to control or adjust the partial pressure of xenon on the gas side of the membrane, including gas lines, valves, sensors... Such devices or systems are well known in the art.
  • the second partial pressure of xenon (pXe2) applied or maintained on the gas side of the at least one membrane is greater than or equal (pXe2 > pXel), the first partial pressure of xenon (pXel) in the blood on the liquid side of the at least one membrane.
  • a third xenon-containing gas may also be administered by inhalation to the patient after the CPB operation.
  • this gas is preferably a xenon-containing gas having a volume amount of xenon from between 5 and 75 volume %.
  • the first partial pressure of xenon is achieved by administering xenon-containing gas to the patient via inhalation, for example using a respiratory mask or an intubation probe, and this level is maintained either utilizing the partial pressure embodiment disclosed below or the selective membrane embodiment disclosed below.
  • xenon is administered in combination with one or more other gases, such as oxygen
  • the xenon and other gas(es) can be administered in a variety of manners, preferably by inhalation of a mixture of all of the gases at once.
  • using xenon in lieu of CFC compounds makes it possible to avoid the problems and risks linked to rapid changes of blood temperature of the patient that typically happen during a CPB procedure.
  • the vapour pressure of gaseous xenon equals about 50 bar at 16°C and about 80 bar at 40 0 C.
  • the increase of gaseous volumes during CPB is a maximum of 10% of the increase of gaseous volumes obtained with volatile anaesthetics, especially CFC compounds as above explained.
  • Another advantage of using xenon over intravenous or volatile substances is that xenon preserves patient blood pressures. Indeed, using xenon for anaesthesia, during a CPB procedure, although being known to have less side effects on cardiac pumping function, cerebral vascular function (i.e. preservation of autonomous blood pressure regulation of the brain (cerebral autoregulation)) was never taken into account.
  • the introduction of closed systems using xenon during CPB procedures makes possible the use of xenon during the CPB phases, as shown on Figure 3, i.e. during the pre-CPB phase, the post-CPB phase and also during the CPB phase itself.
  • the different embodiments of the present invention are based on the use of xenon during cardiac surgery, ECMO or similar procedures, especially during the CPB phase, in anaesthetic concentrations (volume %) from about 5% to about 75%, depending on the age, gender and intra operative body temperature of the patient and on the amount and types of co-administered drugs.
  • xenon allows for a decrease in the quantity of required additional drugs to be co-administered. This in turn reduces the adverse effects of those agents while at the same time preserving blood pressures, cerebral auto-regulation of perfusion pressure and cardiac output capabilities.
  • At least an additional anesthetic agent can be administrated to the patient.
  • Said additional anesthetic agent can be at least a volatile compound to be inhaled by the patient chosen among sevoflurane, desflurane, isoflurane and enflurane.
  • the amount of said volatile compound to be inhaled by the patient typically constitutes from between 0.05 vo 1.% and 15 vol. %.
  • the additional anaesthetic agent can also be at least an injectable compound chosen among opiods or syntethic opioids, hypnotic acting agents like propofol, benzodiazepines, such as midazolame, flunitrazepame or diazepame, barbiturates, like thiopentone or pentobarbital, and any other hypnotic acting agents.
  • the amount of said injectable compound utilized is between the lowest efficient amount and the maximum dosage before over dosage, i.e. the individual limit to its over-dosage.
  • the most suitable amount should be determinate by the physician depending on the parameters of the patient to be treated, such as his age, weight, gender, co-medication(s), concomitant disease, depth of anesthesia as measured using clinical signs, electroencephalographic parameters, parameters using the patients general oxygen consumption or the patient's brain's oxygen consumption as parameters for the depth of anesthesia.
  • the method utilized involves the administering of xenon to the patient via inhalation (pre-CPB) followed by maintaining the level in the blood via partial pressure or selective membranes (during CPB), the patient is first administered an effective amount of xenon in the form of a xenon-containing gas.
  • effective amount means an amount of xenon that is effective in producing the desired effect of anesthesia, for instance an amount which is sufficient in the patient to induce anesthesia.
  • the xenon-containing gas(es) utilized in the present invention (whether the first, second or third xenon-containing gas) contain a preferred volume amount of xenon from between 15 vol. % and 79 vol. %, preferably from between 40% and 79% vol. %, before CPB and a preferred volume amount of xenon from between 15 % and 79 vol. %, preferably from between 20 and 59 vol. %, during and after the CPB phase.
  • the inhaled xenon-containing gas preferably comprises a mixture of oxygen and xenon with the mixture containing from between 18 % and 90 % of oxygen, preferably between 20 % and 65 % of oxygen, even more preferably from 20 % to 40% of oxygen.
  • the proportion of gaseous xenon in the gas mixture will typically be from between 5 and 75% volume.
  • the xenon-containing gas comprises a mixture of oxygen and xenon
  • the xenon-containing gas may be obtained in a variety of manners.
  • the xenon and oxygen may be mixed at the appropriate concentrations prior to the gas being introduced into the heart-lung machine (premixed cylinders).
  • the xenon and oxygen may be injected as separate steams into the heart-lung machine which will provide a means of mixing the two gases within the machine before they are brought into contact with one or more CPB membranes.
  • the CPB machine will comprise at least two separate membranes, one for allowing the diffusion of xenon into blood and another for allowing the diffusion of oxygen into the blood and CO 2 out of the blood, each membrane located in a separate compartment.
  • an oxygen stream will be injected into a first compartment that houses the membrane that allows for the diffusion of oxygen into the blood and CO2 out of the blood. This oxygen will be allowed to contact the membrane on one side while the blood from the patient contacts the membrane on the other side of the membrane. Blood treated in this manner will then pass through a separate compartment which contains a membrane which will allow for the diffusion of xenon into the patient's blood. In this compartment, a stream of xenon will be allowed to contact the membrane on one side while the blood from the patient contacts the membrane on the other side of the membrane.
  • the order of the two compartments is reversed. In many instances, prior to the CPB phase, the patient is pre-medicated with a xenon-containing gas.
  • the blood extracted from the patient will already include a certain concentration of xenon and the other gases contained in the xenon-containing gas.
  • blood is extracted from a patient's body utilizing a heart-lung machine.
  • the blood is extracted from the patient's body, it is pumped through the heart- lung machine and where it is brought into contact with the CPB membrane(s) thereby allowing for the reintroduction of xenon and other gas (i.e., oxygen) and the removal Of CO 2 and then at least a part of the patient's blood that contains adjusted levels of xenon and oxygen is reintroduced by the heart-lung machine into the patient's body.
  • xenon and other gas i.e., oxygen
  • the patient is put in a state of hypothermia. That is to say, the temperature of the body of the patient is decreased to less than 35 0 C, typically from between 30 0 C to 35 0 C, and maintained at that temperature or within this temperature range during at least a part of the CPB phase.
  • First embodiment of the invention partial pressures
  • a non-selective membrane separates the gaseous side of the CPB system from the liquid side (blood side).
  • Xenon and the other compounds, in particular O 2 and CO 2 normally pass freely through the membrane, from the gas side towards the liquid side, and/or vice versa.
  • the xenon concentrations on the gas side of the membrane will range from about 10 ppm to about 80 vol. %. It is important to keep a partial pressure of xenon on the gas side of the membrane that is very close or higher than the partial pressure of xenon in the blood, i.e., on the liquid side of the membrane. This is necessary in order to block or limit the diffusion of xenon from the liquid (blood) side of the membrane towards the gas side of the membrane thereby limiting the loss of xenon.
  • a xenon partial pressure that is sufficient to obtain and maintain anaesthesia.
  • a partial pressure of xenon of about 70% means about 70% of
  • oxygen partial pressure in the blood should be kept above low limits, i.e. above about 21 vol. %.
  • normal oxygen blood tension is from 21% to 100% of 760 mm Hg, from which should be deduced the partial pressure of the other gas(es) dissolved in the blood, i.e. typically CO 2 since CO 2 molecules replace O 2 molecules in the blood.
  • CO 2 has a partial pressure of about 40 mm Hg in the blood entering in the heart-lung machine, at room temperature (i.e. about 25°C)
  • an oxygen tension of 21% corresponds to an oxygen partial pressure of about 110 mm Hg (i.e. 21% x 760 mm Hg - 40 mm Hg). This shows that oxygen partial pressure does not change when oxygen tension is
  • the partial pressure of xenon is from about 500 to 530 mm Hg.
  • xenon partial pressure will change if oxygen is added to the blood in concentrations higher than 21 %, i.e. if the oxygen partial pressure is increased.
  • the resulting partial pressure of xenon in the blood will only be 340 mm Hg (i.e. 760 mm Hg - 420 mm Hg) in lieu of about 500 mm.
  • the partial pressure of xenon in the blood varies when the concentration of oxygen in the blood varies.
  • the partial pressure of xenon on the gas side of the membrane will be kept higher than the partial pressure of xenon found in the blood, i.e. on the liquid side of the membrane.
  • the membrane to be used during the CPB phase in the present invention can be any non-selective membrane which is capable of allowing the passage of xenon into the blood.
  • Such non-selective membranes are preferably hollow fiber-type membranes or flat sheets made of various materials, either porous or non-porous, and include, but are not limited to, membranes made of silicone, bisphenol, sulfone, carbonate, polysulfone, polycarbonate, cellulose (acetate), copolymidine, ethylo cellulose, polyamide nylon, polyethersulfone, polyimide, polypyrrolone, polyvinyl acetate or any other suitable material.
  • the membrane is a hollow fiber-type membrane with the gas side of the membrane comprising the internal or external part of the fibers. Such membranes are readily known in the art.
  • a selective membrane separates the gaseous side of the CPB system from the liquid side or blood side.
  • selective membranes separate gas mixtures allowing at least one of the compounds in the gas mixture to diffuse more or less freely through the material that constitutes the membrane, whereas one or more of the others compounds in the gas mixture are almost totally, if not completely, retained, i.e. do not diffuse through the membrane.
  • different gaseous compounds pass through a selective membrane at different rates and time constraints.
  • the selective membrane to be used during CPB should allow a free exchange of O 2 and CO 2 molecules between its gas side and its blood side for O 2 , and vice versa for CO 2 , but should at the same time, block or at least limit the passage or diffusion of xenon from the blood side to the gas side in order to decrease the loss of xenon in the waste gases that are subsequently vented.
  • Choosing such a selective membrane for use in the framework of the present invention can be done empirically via routine testing by a physician as the diffusibility of xenon through such membranes is readily known. Using such a selective membrane will indirectly lead to the control of the partial pressure of xenon in the blood thereby minimizing the loss of xenon while at the same time maintaining an adequate level of xenon for ensuring efficient anesthesia during the CPB phase.
  • Nanocarbone membranes that can be used in the method according to the present embodiment of the invention are nanocarbone membranes.
  • Such nanocarbone membranes allow a free transfer of oxygen and CO 2 , which must be exchanged during the CPB procedure (which is the typical work of the lung) but limit the passage of xenon from the blood side to the gas side.
  • PMP poly-methyl-pentene
  • NC - nanocarbone carbon with engraved filtration capillaries
  • the selective membranes for use in the present invention are preferably hollow fibre-type membranes or flat sheet-type membranes, although other types of membranes are not excluded from the present invention.
  • the membrane When the membrane is a hollow fiber-type membrane, it preferably has a gas side of the membrane that comprises the internal or external part of the fibers.
  • Xenon selective membranes are preferably used during the CPB procedure, like cardiac surgery or ECMO, in which xenon has been administered to the patient already before the start of the CPB procedure by means of a conventional ventilation of the lungs (inhalation utilizing any known means of administering gases).
  • a selective membrane can be combined with an adjustment of the partial pressure of xenon on the gas side of the membrane as above described in the first embodiment.
  • xenon gas has to be administered into the membrane system, i.e. the oxygenator, to compensate for the loss of xenon due to a permeation of small amounts of xenon through the membrane material. This will occur even in highly selective membrane materials.

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  • Health & Medical Sciences (AREA)
  • Emergency Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un appareil et une méthode destinés à maintenir ou à fournir une anesthésie pour un patient en train de subir une procédure de circulation extracorporelle (CEC), comprenant les étapes consistant à : extraire du corps du patient au moins une partie de son sang, ledit sang contenant une première pression partielle de xénon; faire circuler le sang extrait à travers un cœur-poumon artificiel comprenant au moins une membrane pourvue d'un côté liquide et d'un côté gazeux; mettre en contact un gaz contenant du xénon avec le côté gazeux de la membrane du cœur-poumon artificiel, tout en mettant en contact simultanément le sang du patient circulant à travers le cœur-poumon artificiel avec le côté liquide de la membrane; appliquer ou maintenir une seconde pression partielle de xénon sur le côté gazeux de la membrane; et réintroduire, dans le corps du patient, le sang contenant du xénon provenant du cœur-poumon artificiel et ayant été en contact avec la membrane.
EP09783487A 2008-10-06 2009-09-28 Anesthésique gazeux à base de xénon destiné à être administré par le biais d'un c ur-poumon artificiel Withdrawn EP2344219A1 (fr)

Applications Claiming Priority (2)

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US10296008P 2008-10-06 2008-10-06
PCT/EP2009/062528 WO2010040656A1 (fr) 2008-10-06 2009-09-28 Anesthésique gazeux à base de xénon destiné à être administré par le biais d'un cœur-poumon artificiel

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EP2344219A1 true EP2344219A1 (fr) 2011-07-20

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FR2964876B1 (fr) * 2010-09-22 2013-04-12 Air Liquide Sante Int Composition anesthesique gazeuse a base de xenon utilisable pendant une endarteriectomie avec clampage de l'artere carotide
DE102013112523A1 (de) * 2013-11-14 2015-05-21 Technische Universität Dresden Verfahren und Vorrichtung zum Einstellen der Mengenanteile unterschiedlicher Gase in einer Flüssigkeit
WO2018106164A1 (fr) * 2016-12-08 2018-06-14 Maquet Critical Care Ab Système d'élimination de co2
MX2021011523A (es) * 2019-03-25 2021-12-15 Mallinckrodt Pharmaceuticals Ireland Ltd Sistema de suministro de gas.
RU2726048C1 (ru) * 2019-11-11 2020-07-08 Федеральное государственное бюджетное учреждение "Федеральный Сибирский научно-клинический центр Федерального медико-биологического агентства" Способ лечения хронической боли

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DE10045829A1 (de) 2000-09-14 2002-04-04 Messer Griesheim Gmbh Volatile Anästhesiemittel mit Xenon
CA2430304A1 (fr) 2000-11-28 2002-06-06 Art Of Xen Limited Echange gazeux
DE102004015406A1 (de) * 2004-03-26 2005-10-13 Ino Therapeutics Gmbh Verfahren und Vorrichtung zur Administration von Xenon an Patienten
DE102006034601B3 (de) * 2006-07-26 2008-02-07 Schmidt, Klaus, Prof. Dr. Rückhaltung von Edelgasen im Atemgas bei beatmeten Patienten mit Hilfe von Membranseparation
EP1980260A1 (fr) * 2007-04-10 2008-10-15 Nicholas Peter Franks Utilisation de conditions hyperbares pour fournir une neuroprotection

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