WO2004089444A1

WO2004089444A1 - Apparatus and method particularly for substituting closed circuit elements for extracorporeal circulation

Info

Publication number: WO2004089444A1
Application number: PCT/IB2004/001257
Authority: WO
Inventors: Cesare Strisino
Original assignee: Crb Nederland B.V.
Priority date: 2003-04-08
Filing date: 2004-04-06
Publication date: 2004-10-21
Also published as: ITMI20030696A1; EP1610844A1; RU2005134352A

Abstract

An apparatus and a method particularly for substituting one or more active elements of circuits for extracorporeal circulation (ECC), circuits for extracorporeal respiratory support with membrane oxygenation machine (ECMO), or other similar systems. In particular, the element is preferably selected from the group that consists of the oxygenation chamber (15) and the heat exchanger (16). Preferably, the present invention relates to an apparatus and a method for substituting elements of ECC circuits without interrupting circulation, for example if the maximum utilization times of the elements as stated by the manufacturer are exceeded.

Description

APPARATUS AND METHOD PARTICULARLY FOR SUBSTITUTING CLOSED CIRCUIT ELEMENTS FOR EXTRACORPOREAL

CIRCULATION

Technical field The present invention relates to an apparatus and a method particularly for substituting one or more elements for example of circuits used for extracorporeal circulation (ECC), circuits for extracorporeal respiratory support with membrane oxygenation machine (ECMO), or other similar systems. Background of the invention

Substitution or support of vital functions such as the cardiac, pulmonary or cardiopulmonary function during surgery are now possible for example by using devices that allow extracorporeal blood circulation (hereinafter ECC). These devices are formed by multiple modules, constituted substantially by a circuit of tubes that connect the patient to a blood collection reservoir, a pump capable of supporting the blood flow, an oxygenation chamber provided with a heat exchanger, systems for filtering any unwanted aggregates, and systems for eliminating any bubbles present in the circuit; these devices allow to substitute the cardiopulmonary function for a limited number of hours indicated by the manufacturer.

By using circuits that allow ECC, venous blood is diverted through the right venous access (i.e., the right atrium of the heart, the vena cava, et cetera), and by means of a pump is directed to the oxygenation machine. The oxygenated and cooled or heated blood is then returned to systemic circulation through the arterial access (i.e., the aorta, the femoral artery, et cetera).

Devices that allow ECC can be used only for the times set by the manufacturer and indicated in the operating manuals. This operating time limitation relates not only to the extrapulmonary circulation system in general but also to certain components whose functionality deteriorates over time and elements such as for example the oxygenation machine, the heat exchanger and the arteriolar filter.

Accordingly, if surgical procedures require ECC lasting longer than such recommended time, the oxygenation section of the device may undergo clogging or just a gradual loss of efficiency; this phenomenon becomes evident in terms of variations of respiratory blood parameters (such as arterial oxygen saturation, arterial oxygen partial pressure, et cetera) that can be measured by way of analytical tests (for example hemogas analysis) and in terms of a variation of the values of the pressure that can be measured at the input and output of the oxygenation chamber (such as a drop in output pressure and a rise in input pressure). This loss of efficiency of the oxygenation system, together with the reduction of the pressure in output from the system, are risky events, since they do not allow ECC to support the patient adequately.

The phenomenon of oxygenation machine clogging and of the consequent output pressure drop can occur sometimes also during the initial steps of extracorporeal circulation.

In the case of extracorporeal circulation during patient hypothermia, cryoprecipitates, such as cryofibrinogen or other coagulation factors, sometimes form; these factors deposit at the level of the heat exchanger during patient blood cooling, clogging the cooling/oxygenation system.

Replacement of the oxygenation chamber and/or of the heat exchanger is to be considered as an emergency procedure, due to the complexity and risks normally linked thereto, and consists of a procedure that is feasible depending on the extent to which the functionality of the oxygenation chamber and/or of the heat exchanger has been compromised, on the dimensions and graduality of the clogging, and on the location of the clogging that has formed. Known systems currently applied for example to ECC are composed of a point 1 for drawing venous blood from the patient, termed venous access, the extracorporeal circulation circuit, and the point 2 where the oxygenated and heated or cooled blood is returned to the patient, known as arterial access. The circuit is provided with adapted tubes 3, which convey the blood from the venous access 1 to a blood collection container 4 by means of a pump 5 inserted in the circuit, which can be for example of the peristaltic, centrifugal or other type.

Blood arriving from other points not shown in Figure 1, such as for example from the operating field or from blood bags, can reach said container 4; said container can also receive other known blood and plasma replacement fluids.

From the collection container 4, the blood propelled by the pump 5 passes, through a line constituted by an adapted tube 6, to the oxygenation chamber 7 and/or to the heat exchanger 8.

From the oxygenation chamber 7 and/or heat exchanger 8, the blood passes, through an adapted tube 9, to a filtration system 10 for eliminating any air bubbles and/or unwanted aggregates, and then returns to the patient 11 by means of a suitable tube 12 and the arterial access 2. The system is further provided with a line 13 for eliminating any air bubbles present in the oxygenation machine 7 and/or heat exchanger 8, wherein said line 13 starts from the oxygenation machine 7 and/or heat exchanger 8 and is connected to the blood collection container 4.

Another element of said circuit is constituted by a line 14 that connects the arteriolar filter 10 to the blood collection container 4 in order to eliminate any air, i.e., air bubbles, present therein.

Other accessory elements, not shown in Figure 1, may be added to the extracorporeal circulation circuit described above.

Moreover, it is known that during extracorporeal circulation there may be additional devices and circuits that perform several functions, such as for example an apparatus with a corresponding pump and circuit for decompressing the right ventricle, and an apparatus and a corresponding pump and circuit for optional cardioplegia, an apparatus and an associated pump and circuit for intraoperative recovery of blood from the operating field, and additional devices.

Currently, the known method for substituting the oxygenation machine 8 and/or the heat exchanger 7 provides for the following steps: ~ working at all times in aseptic conditions, keeping the first oxygenation machine 8 and/or heat exchanger 7 in use until the second unit is ready for use;

~ preparing the backup unit by manually setting up the necessary sections of tube in input and in output on the new oxygenation machine and/or heat exchanger;

~ then filling the backup unit by using the volume contained in the active extracorporeal circuit, after checking that the volume contained therein is sufficient. If it is not, an adequate quantity of suitable liquids, such as blood, plasma or substitutes thereof, is added;

~ removing the active unit, the accessories and the lines that are no longer necessary and keeping the pump active, closing the input and output tubes of the backup oxygenation machine and/or heat exchanger by using additional clips;

~ at this point, stopping the arterial pump and therefore interrupting extracorporeal circulation; then, by using two clips, closing the tube comprised between the pump and the inlet of the active unit, cutting and then manually connecting, while avoiding the trapping of air bubbles, the tube downstream of the pump to the backup unit; a similar action is provided between the outlet of the active unit and the arterial filter, with subsequent connection, also performed manually, to the backup unit;

~ the arterial pump and extracorporeal circulation can be reactivated only after performing the maneuvers described above, and this is done slowly at first, subsequently returning to the intended flows. The operating sequence described so far clearly indicates the presence of many limitations linked to it. For example:

~ the standard procedure for substituting the oxygenation machine, in view of the complexity and the time required for its execution, in practice does not lend itself to substitution of the oxygenation machine as a routine procedure in situations such as the expiration of the operating time of the oxygenation system and/or heat exchange system stated by the manufacturer. Accordingly, the oxygenation machine might be used for longer than the stated times, with evident risks linked to an improper use of the product;

~ substitution of the oxygenation machine according to the standard procedure is possible in practice only during operations with patient hypothermia, since in normothermia the time required for substitution and the expected temporary interruption of ECC are not compatible with patient survival, causing high risks of irreversible damage to vital organs;

~ the maneuvers to be performed during the standard procedure are particularly invasive and rudimentary, since they are linked to manual cutting of the lines for connection to the oxygenation machine and/or heat exchanger in use, exposing the patient and the operator to risks of contamination;

— the standard procedure requires the operator to perform manually the connections of the various tubes, accurately avoiding the presence of bubbles in the circuit;

~ the complexity of the connections in this case does not assist the operator, who in practice relies on empirical methods in order to try to reduce the probability of introducing bubbles in the circuit;

— many manufacturers require the oxygenation machine substitution procedure to be performed by two operators, who in practice are not always available; ~ the maneuvers to be performed during the standard procedure are particularly awkward and require an execution time that depends on the body temperature of the patient at substitution time. For example, at 30 °C, stopping circulation is allowed for no more than 3 minutes, but uniformly reducing the temperature from 37 to 30 °C in a 70-kg person requires more than this time; ~ the standard procedure for substituting the oxygenation machine and/or heat exchanger always provides for the stopping of the arterial pump, i.e., for the interruption of extracorporeal circulation for the time required for substitution, with consequent possible tissue damage; ~ the performance of the system that supports blood oxygenation and/or patient body temperature variation is inversely proportional to the increase in the execution time of the surgical procedure, and accordingly the patient suffers due to inadequate blood perfusion when the operation lasts longer than the operating times recommended by the manufacturer; ~ the performance of current systems does not allow to modulate the oxygenation machine and/or heat exchanger. By way of example, for patients with high body weight (for example over 110 kg), the oxygenation and/or heat exchange system might be inefficient or insufficient with respect to the requirements of the patient; ~ the existence of double-chamber systems for the oxygenation machine and/or heat exchanger entails oversizing the priming volume of the device, with increased dilution of the blood of the patient;

~ the standard procedure for substituting the oxygenation and/or heat exchanger depends entirely on the operator, with the associated variables caused both by the operator himself and by the various situations in which the operator has to work (such as the availability of a second support operator, particularly conditions of the patients requiring specific times or other parameters, et cetera); ~ the standard procedure for substituting the oxygenation machine and/or heat exchanger currently provides for interrupting extracorporeal circulation for critical times (approximately 6-7 minutes); this extracorporeal circulation interruption can be performed so as to minimize patient damage only during operations performed in hypothermia and is instead incompatible with operations performed in normothermia. Another method known as extracorporeal respiratory support with membrane oxygenation machine (hereinafter ECMO), which can be performed for extended times, in its modified form of heart-lung bypass, has clogging limitations similar to those described earlier for ECC.

The limitations noted above have not currently been overcome even by other known examples of extracorporeal circulation, such as for example: ~ ECLS, or emergency extracorporeal life support;

~ ECLA, or extracorporeal support of the respiratory function or extracorporeal lung assist; — ECCOR, or extracorporeal C0₂ removal;

~ ECPR, or emergency extracorporeal cardiopulmonary function support or extracorporeal cardiopulmonary resuscitation;

~ extracorporeal circulation for assistance and/or support to organs, tissues, areas or specific regions of the body, such as for example a limb, or organs such as the liver or brain; -- locoregional extracorporeal circulation in hyperthermia, for example of a single organ for simultaneous local administration of antiblastic drugs. This respiratory support is performed by applying to a patient that requires it a membrane oxygenation system for relatively long periods (even several days). However, this method provides for periodic substitution of the oxygenation chamber, dealing with problems that can be likened to the ones described for ECC.

Summary of the invention Accordingly, the aim of the present invention is to provide an apparatus and a method for substituting at least one element in closed circuits in use for example for extracorporeal circulation (ECC), circuits for extracorporeal respiratory support with membrane oxygenation machine (ECMO), or other systems that can be likened to these, such as emergency extracorporeal circulation support circuits (ECLS), a circuit for extracorporeal support of the respiratory function (ECLA), a circuit for extracorporeal C0₂ removal (ECCOR), a circuit for emergency extracorporeal cardiopulmonary function support (ECPR), a circuit for extracorporeal circulation to support and/or assist specific organs, tissues, areas, regions of the body, and a circuit for locoregional extracorporeal circulation in hyperthermia, for example of a single organ for simultaneous local administration of antiblastic drugs, that overcomes the drawbacks of the background art.

Within this aim, an object of the present invention is to provide an apparatus and a method that are simple, rapid and safe for substituting at least one element, preferably the oxygenation chamber and the heat exchanger, in closed circuits used for example for extracorporeal circulation (ECC), circuits for extracorporeal respiratory support with membrane oxygenation machine (ECMO), or other systems that can be likened to these, such as for example a circuit for emergency extracorporeal circulation support (ECLS), a circuit for extracorporeal support of the respiratory function (ECLA), a circuit for extracorporeal C0₂ removal support (ECCOR), a circuit for emergency extracorporeal cardiopulmonary function support (ECPR), a circuit for extracorporeal circulation to support and/or assist specific organs, tissues, areas, regions of the body, and a circuit for locoregional extracorporeal circulation in hyperthermia, for example of a single organ for simultaneous local administration of antiblastic drugs.

Another object of the present invention is to provide an apparatus and a method for inserting a new element, preferably in a closed circuit in use for extracorporeal circulation (ECC), without interrupting said circulation. This aim and these and other objects are achieved by an apparatus for inserting at least one element in a first closed circuit suitable for extracorporeal substitution or support of vital functions, wherein said apparatus is characterized in that it comprises: ~ said at least one element to be inserted, ~ means adapted to constitute a second circuit that comprises said at least one element to be inserted, said means connecting said element to be inserted in said first circuit. This aim and these objects are also achieved by a method for inserting at least one element in a first closed circuit suitable for extracorporeal substitution or support of vital functions, wherein said method comprises the steps of:

~ connecting to said first circuit an apparatus according to the present invention, said apparatus comprising said at least one element to be inserted and means suitable to constitute a second circuit, said second circuit comprising said apparatus inserted in said first active circuit,

-- diverting the blood flow from the first closed circuit into said second circuit, optionally isolating at the same time part of the first circuit, said isolated part comprising an element that is functionally identical to said at least one inserted element, wherein said steps occur during blood perfusion of said first circuit and said perfusion is never halted.

According to the present invention, the element to be inserted is preferably selected from the group that consists of an oxygenation chamber, a heat exchanger, an arteriolar filter, filtration means and bubble elimination means, a blood collection tank, means that support or substitute the blood propulsion system (such as for example a peristaltic pump or a centrifugal pump), manifold access systems for sampling blood for analysis, and recirculation systems.

Likewise, the circuit in which said elements are inserted is for example: — a circuit for extracorporeal circulation (ECC), a circuit for respiratory support with membrane oxygenation machine (ECMO), an ECLS (Extracorporeal Life Support) circuit or emergency extracorporeal circulation support, — an ECLA (Extracorporeal Lung Assist) circuit or extracorporeal respiratory function support; an ECCOR (Extracorporeal C0₂ Removal) circuit or extracorporeal C0₂ removal support; an ECPR (Extracorporeal Cardiopulmonary Resuscitation) circuit or emergency extracorporeal cardiopulmonary function support; a circuit for extracorporeal circulation to support and/or assist specific organs, tissues, areas or regions of the body, such as for example a limb, or organs such as the liver or the brain; a circuit for locoregional extracorporeal circulation in hyperthermia, for example of a single organ for simultaneous local administration of antiblastic drugs, and systems assimilable thereto.

The apparatus according to the present invention further comprises, in a preferred manner, a container that contains a priming liquid and means adapted to connect said container to the other components of said apparatus. The connection means comprised in the apparatus according to the present invention may also advantageously comprise a pump that is suitable for example for moving the priming fluid.

The apparatus according to the present invention preferably also comprises additional elements for eliminating any unwanted aggregates and any bubbles, and means adapted to connect said elements to the other components of said apparatus.

The means adapted for connection according to the present invention may be individual connectors, which advantageously can also be coupled to tubes. Said connectors, optionally coupled to the tubes, also allow to recover the fluid, such as for example blood, that is present as a residue in portions of the first circuit that are isolated as a consequence of the application of the present apparatus.

In particular, said regions or units of said first circuit comprise for example tubes, heat exchangers and oxygenation machines and more generally all those elements of the first circuit that are technically equivalent to the ones that are inserted by using the apparatus according to the invention.

Said connectors, optionally coupled to the tubes, may comprise quick- coupling points, such as for example bayonet coupling points, coupling points having a conical cross-section, and coupling points with a tail piece.

The connection means described here, regardless of their structure, maybe provided independently and be then integrated in the apparatus according to the invention, preferably in the element to be inserted, or can be inserted by the operator on the active line of the first circuit.

Said connection means may instead also be already inserted on the active line of the first circuit.

If the connection means comprise connectors, said connectors are advantageously constituted by systems with three or more ways, provided with a device for manual or automatic shunting of the blood flow that is adapted to divert the circulation from the active line of the first circuit to the apparatus. Preferably, said shunting device consists of at least one ball valve.

If the connection means are to be inserted or are already inserted in the active circuit, they can also be provided with at least one access point in a manifold or series configuration for the insertion of additional elements, and with additional tubes and also with optional sensors for monitoring physical and chemical parameters.

The accurate monitoring of physical and chemical parameters is a particularly important aspect in order to ensure the efficiency of said apparatus. Accordingly, the apparatus according to the invention may also accommodate, in appropriate points, sensors that are adapted to detect physical and chemical parameters, such as for example temperature, pressure, pH, electrolyte concentration, partial pressure of gas, and gas saturation.

In view of its specific use in the medical field, the apparatus according to the invention is advantageously provided by using sterile material or material that can in any case be sterilized at a later time. Said material must also be biocompatible. Materials suitable for manufacturing the present apparatus may be for example biocompatible plastics or plastics that are rendered biocompatible by means of surface treatments.

Particular attention must be given to the biocompatibility of these materials with drugs, molecules, gases or substances that are used during extracorporeal circulation. Moreover, the apparatus according to the invention may be packaged in double packages constituted by an external container that is appropriately sealed and is suitable to preserve the package in an environment that is not necessarily sterile, said container containing one or more secondary packages that are already sterile and can be transported within protected environments and are suitable to be opened when required.

Likewise, since the priming and bubble removal steps may also occur prior to connection of said apparatus to the first active circuit, the apparatus according to the invention may be supplied in an already primed and bubble-free condition. Finally, the apparatus according to the invention may be made to size for the individual user, i.e., with specific characteristics for different types of use and different types of user.

The present invention also relates to a method for inserting at least one element in a first closed circuit suitable to provide extracorporeal substitution or support of vital functions.

Advantageously, in addition to the steps already mentioned, the method further comprises the step of eliminating the bubbles that are present in the second circuit (bubble removal), wherein said step occurs preferably after diverting the blood flow. In an equally advantageous manner, the method further comprises the step of priming said second circuit, and said step preferably occurs between the connection step and the step for diverting the blood flow.

However, in other cases both the bubble removal step and the priming step may occur before connecting the apparatus to the first active circuit, so that said apparatus can also be supplied in an already bubble-free and primed condition.

The circuit priming step can occur either by transferring into the second circuit the blood contained in the blood collection container that belongs to the first circuit or by transferring into the second circuit a priming liquid that is contained in a container that is not part of the first circuit.

In the second case cited above, transfer occurs for example by gravity or by means of a pump.

The method according to the present invention has proved to be surprisingly useful for example if the insertion of said element is needed as a consequence of clogging or wear of an element that is part of the first circuit and is technically equivalent to the one to be inserted.

Finally, a third aspect of the present invention relates to the unexpectedly optimum use of an apparatus described above in a treatment of the pediatric type. In view of what has been described above, a first preferred configuration of the present invention relates to an apparatus that is constituted by an oxygenation machine that is advantageously coupled to a heat exchanger, both devices being provided with means, such as for example connectors, suitable for coupling on a line of the ECC.

Said extracorporeal circulation line is provided with connectors suitable for the coupling of the new apparatus.

Said apparatus also has corresponding tubes that can be connected to a container that contains the liquid required to fill the apparatus and eliminate any bubbles.

The invention is preferably but not exclusively dedicated to use during ECC, when it is necessary to substitute or even only add a further oxygenation machine and/or heat exchanger. Preferably, this can occur in cases of partial or total malfunction of the active oxygenation machine and/or heat exchanger or if the maximum operating times stated by the manufacturer are exceeded, or if it is necessary to provide greater support of the oxygenation and/or temperature control function (for example with obese patients).

The invention allows for example to substitute or even just add a new oxygenation machine and/or heat exchanger, taking a time that is negligible with respect to the method currently in use and applying a procedure that is simple and safe and does not require interruption of ECC and therefore can be applied for example also to operations performed in patient normothermia conditions. This possibility of use is far more extensive than the current situation, in which the standard procedure for substituting the oxygenation chamber and/or heat exchanger can be performed only in patient hypothermia condition during heart surgery.

The invention further allows to avoid cutting and connecting manually the circuit in points where blood flow is present during ECC, thus avoiding the exposure of the patient and of the operator to risks of infection; the invention further allows better management of operating spaces, which are already confined due to the presence of many devices.

The apparatus and the method according to the present invention therefore allow the rapid replacement or even just the addition of an oxygenation chamber and/or of the heat exchanger in apparatuses for extracorporeal circulation (ECC) and/or extracorporeal respiratory support with membrane oxygenation machine (ECMO) and/or another similar system, such as emergency extracorporeal circulation support circuits (ECLS), circuits for extracorporeal support of the respiratory function (ECLA), circuits for extracorporeal C0₂ removal (ECCOR), circuits for emergency extracorporeal cardiopulmonary function support (ECPR), circuits for extracorporeal circulation to support and/or assist specific organs, tissues, areas, regions of the body, and circuits for locoregional extracorporeal circulation in hyperthermia, for example of a single organ for simultaneous local administration of antiblastic drugs.

The apparatus and the method according to the invention may in any case also be used in other fields of application requiring rapid substitution in closed circuits of at least one component that has deteriorated or is in otherwise inadequate or even just scarcely efficient. These further applications allow to maintain the advantage of the connection of new components without interrupting the operation of the existing circuit and without introducing air in said circuit.

The invention described in its application in extracorporeal circulation provides for its use by health workers responsible for extracorporeal circulation, i.e., perfusionists, who do not require particular training to use the invention. Moreover, the invention is designed so as to make it quick and safe to use and so as to lack critical points and risks of error.

Moreover, the system limits contamination of the environment, of the operators and of the patient with blood and other potentially infected material.

The invention, thanks to its simplicity of use, safety and rapidity, also allows to develop and use new oxygenation systems and/or heat exchangers with characteristics of high efficiency but with a low maximum operating duration, thus allowing to have multiple substitutions of said elements available during operations that use ECC, ECMO circuits and other similar circuit systems.

The present invention also relates to a new method for substituting the oxygenation machine and/or heat exchanger that avoids manually cutting the circuit in points where blood flow is present by virtue of the preinsertion in the active circuit of means, preferably sterile connectors, that are suitable to allow to save time in connecting the new circuit and to provide a reduced risk of contaminations for the patient and the operator.

The invention allows to perform the procedure without interrupting ECC.

The invention allows to eliminate any bubbles and unwanted aggregates rapidly, simply and safely.

The invention can be provided and applied to all currently used extracorporeal circulation systems. Manufacturers of oxygenation machines and/or heat exchangers state and guarantee the functionality of these systems for a specific time (usually 6 to 8 hours). The invention instead allows to substitute the oxygenation machine and/or heat exchanger when the maximum stated operating time guaranteed by the manufacturer expires, by performing a procedure that is simple, quick and safe and does not interrupt ECC.

Manufacturers of oxygenation machines and/or heat exchangers state and guarantee the operation of said systems for the support of patients up to a specific weight (up to 110 kg). The invention instead allows to add, for example in a parallel configuration, at least one oxygenation machine and/or heat exchanger, adapting the oxygenation and/or heat exchange capacity to the patient according to the characteristics of the oxygenation machine and/or heat exchanger stated and guaranteed by the manufacturer, by performing a procedure that is simple, quick, safe, and does not interrupt ECC. In a preferred embodiment, substituting exclusively the oxygenation chamber and/or the heat exchanger avoids substituting the blood tank, thus allowing better management of operating spaces, where the spaces are already confined due to the presence of many devices.

The invention can be produced and applied also to substitute and/or add other components, such as for example the arteriolar filter, that are part of an extracorporeal circulation system or of other closed circuits.

By way of non-limiting example, mention is made of the possible application of the invention during extracorporeal respiratory support with membrane oxygenation machine (ECMO) for prolonged times, in its modified form of heart-lung bypass .

Brief description of the drawings Further characteristics and advantages of the present invention will become better apparent from the description of preferred but not exclusive embodiments of the apparatus and the method according to the present invention, wherein:

Figure 1 is a diagram of an apparatus for extracorporeal circulation according to the prior art;

Figure 2 is a diagram of an apparatus according to the invention, in which the connectors are not preassembled in the existing circuit; Figure 3 is a diagram of an apparatus according to the invention, in which the connectors are preassembled in the existing circuit and the apparatus is primed by means of a liquid that arrives from a blood collection container of the existing circuit;

Figure 4 is a diagram of an apparatus according to the invention, in which the connectors, configured in a manifold or series configuration, in order to provide additional accesses to the system, are preassembled in the existing circuit and the apparatus is primed by means of a liquid that arrives from a blood collection container of the existing circuit;

Figure 5 is a diagram of an apparatus according to the invention, in which the connectors are preassembled in the existing circuit and the apparatus is primed by means of a liquid contained in a pouch that is connected by a tube to the apparatus according to the invention;

Figure 6 is a diagram of an apparatus according to the invention in which the connectors are preassembled in the existing circuit and the apparatus is primed by means of a liquid contained in a pouch that is connected by a tube to the apparatus according to the invention and in which said liquid is propelled by a pump that serves the pouch;

Figure 7 is a diagram of the active circuit connected to the invention, illustrating a variation of the method for inserting and priming the invention;

Figure 8 is a diagram of the active circuit connected to the invention, illustrating a variation of the method for inserting and priming the invention;

Figure 9 is a diagram of the active circuit connected to the invention, illustrating a variation of the method for inserting and priming the invention.

Ways of carrying out the invention The following non-limiting exemplifying description of an apparatus and of a method according to the present invention relates to application to a generic extracorporeal circulation. Example 1

The present invention, which allows substitution and/or addition of the active oxygenation chamber 7 and/or heat exchanger 8, comprises the following elements (see Figures 2 to 9): — an oxygenation chamber 15, with or without the heat exchanger 16; two lines 17 and 18 of suitable diameter, respectively at the input and at the output, which connect the oxygenation chamber 15 and/or the heat exchanger 16 to two connectors 19 and 20, said lines being optionally provided with coupling points 21 and 22; two connectors 19 and 20, which are provided with a ball valve or another type of valve or flow shunting device, adapted to shunt the flow from the active lines 6 and 9 to the new lines 17 and 18; said connectors 19 and 20, which are already inserted (Figures 3 to 9) or can also be insertable (Figure 2) in the extracorporeal circulation system upstream and downstream of the oxygenation chamber 7 and/or the heat exchanger 8; said connectors 19 and 20, each optionally provided with three coupling points, designated by the reference numerals 23, 24, 27 and 25, 26, 28 respectively. Two coupling points, respectively 23 and 24, are for the connector 19, and two points 25, 26 are for the connector

20, so as to allow connection of the tubes required for the conventional extracorporeal circulation line 6 and 9. One coupling point, respectively the point 27 for the connector 19 and the point 28 for the connector 20, is dedicated to the connection of new tubes 17 and 18, which are lines that can be inserted without interfering with the flow of blood along the active line 6-9, accordingly avoiding interruption of the flow (Figures 2 to 9); said connectors 19 and 20, by virtue of the presence of a ball valve or of another type of valve or shunting device, allow to shunt the blood flow from the active lines 6 and 9 to the new lines 17 and 18 by activating the ball valve or other type of valve or shunting device (Figures 2 to 9); said connectors 19 and 20 have laterally adjacent further coupling points, such as the suitable connectors 38, 39, 40 and 41, which are also provided with a ball valve or with flow shunting devices, shown schematically in a configuration known as manifold or series for the optional connection of multiple supplemental or backup lines, which can be applied by way of non-limiting example to extracorporeal respiratory support with membrane oxygenation machine (ECMO) for prolonged times in its modified form of heart-lung bypass, and also by virtue of the coupling to suitable tubes that allow to recover the fluid, such as for example blood, that is present as a residue in the unit/units of said first circuit substituted by the apparatus according to the invention (Figure 4). ~ said connectors 19 and 20, which allow to maintain the flow of blood by having one or more valves that isolate the coupling points 27 and 28 for connecting new tubes, allow to direct the blood in the intended direction after connection to corresponding accesses of suitable diameter 23, 24, 25, 26, arranged on lines 6 and 9 in the existing extracorporeal circulation circuit (Figures 2-9). an optional line 30 having a suitable diameter and provided with suitable connections 31 and 32, which can be connected or is already connected to a pouch 33 that contains a suitable fluid for filling/priming the circuit shown in the invention (Figures 5, 6, 8, 9); — an optional pump 34, which is or can be inserted on the line 30 and has a suitable diameter for moving the fluids for filling/priming the circuit shown in the invention (Figures 6, 8, 9). a draining line 29 having a suitable diameter, in which the ends are provided with an optionally one-way valve 35 and with a connection 36 to the blood collection container 4 (Figures 2-9); a cock 37 with a suitable connection for controlling the flow of the liquid contained in the pouch 33 (Figures 5, 6, 8, 9). Further configurations of the invention preferably also include bubble elimination systems for filtering any unwanted aggregates, additional tubes for the recovery of fluids, such as for example blood, possibly present in the element substituted in the existing extracorporeal circulation circuit referenced as first circuit, at least one support for positioning the individual components, and optional connectors for connecting additional lines that are dedicated to sensors for detecting physical or chemical parameters in order to monitor them, and additional tubes for subsequent connections.

The present invention, thus structured in a single-use circuit (Figures

3 to 7 and 9), by applying procedures that are dedicated to it, instead allows to substitute and/or complement a new oxygenation machine 15 and/or heat exchanger 16 with respect to the ones already in use 7 and 8 without interrupting the flow of blood.

Example 2

The method according to the invention allows to exclude simply and safely the active oxygenation machine and/or heat exchanger 7 and 8, allowing to divert the flow toward the new oxygenation chamber 15 and/or heat exchanger 16, simply by connecting the single-use circuit constituted by the invention by means of the lines 17 and 18 (Figures 2 to 9).

In the method according to the invention, the lines 17 and 18, respectively in input and in output to the new oxygenation machine 15 and/or heat exchanger 16, are connected respectively to the suitable connection points 27 in input and 28 in output on the suitable connectors 19 and 20, by connection and optional clamping to the connection points 21 and 22.

The draining line 29 of the new oxygenation machine and/or heat exchanger 15 and 16, preferably provided with a one-way valve 35 and with a suitable connection 36, is then connected to the collection tank 4 in order to allow the operations for eliminating any bubbles of the new apparatus described by the invention (Figures 2 to 4 and 7).

The method that allows the operations for eliminating any air bubbles and the filling/priming of the circuit shown in the variations of the invention that can be referred to Figures 2 to 4 and 7 provides for the following steps: — optionally modulating the speed of the pump 5 without interrupting the flow of blood; ~ opening the suitable connector 19 thus allowing to fill or prime the new apparatus with the liquid contained in the blood collection container 4; in this way, the air that is present is eliminated by means of the draining path 29 provided with an optionally one-way valve 35 and with a suitable connection 36 to the collection tank 4.

Another variation that can be applied to the invention (Figures 5, 6, 8 and 9) and allows the operations for filling, priming and eliminating any air bubbles present in the circuit, uses an additional rapid perfusion path 30, which provides for the following maneuvers.

A coupling 31 is connected to the pouch 33 that contains a liquid that is suitable to prime the circuit described by the invention (Figures 5, 6, 8 and 9); then the cock 37 is opened, allowing the priming liquid to enter the new oxygenation machine 15 and/or heat exchanger 16 due to the difference in head (Figures 5, 8) or by means of a pump 34 that supports its flow (Figures 6 and 9); once filling has ended, the cock 37 is closed and the circuit described by the invention (Figures 6, 7, 10, 11, 12, 13) is freed of bubbles by means of the draining line 29, which is provided with an optionally one-way valve 35 and with a suitable connection 36 to the collection tank 4.

At the end of the bubble removal procedures, the speed of the pump 5 is optionally modulated in order to reduce the blood flow without ever stopping it. The blood flow is then diverted through the connector 19 along the path 17 toward the new oxygenation machine 15 and/or heat exchanger 16 in order to be oxygenated and/or cooled and/or heated, and then the blood flow is diverted, by using the path 18, from the connector 20 to the existing path 9 and then to the arteriolar filter 10, and is then returned, through the path 12, to the patient 11 by means of the arterial access 2 (Figures 8 and 9). Simultaneously, the liquid exits from the draining line 29 toward the collection tank 4 (Figures 8 and 9).

The arteriolar filter 10 ensures the elimination of residual air bubbles in the blood stream directed to the patient 11 by means of the draining line 14 dedicated to it, which conveys said bubbles to the blood collection container 4 (Figures 7-9).

By proceeding in this manner, the safety, simplicity and rapidity parameters required for substitution of the oxygenation chamber and/or heat exchanger are met. The present invention thus described by way of non-limiting example therefore allows to substitute the active oxygenation chamber and/or heat exchanger with a new unit, described in the invention and subsequent variations, by applying procedures that do not require to interrupt the arterial pump and require no manual cutting of the tubes used for the extracorporeal circulation circuit, thus eliminating risks of infection for the patient and the operator.

The present invention further allows repeatability of execution, modulability in adding units that are useful for ECC and/or applicability to particular clinical conditions such as, by way of non-limiting example, extracorporeal respirator support with membrane oxygenation machine (ECMO), for prolonged times, or also the addition of a second oxygenation machine when higher oxygenation and/or heating/cooling of the blood of the patient is required.

The invention thus conceived is susceptible of numerous modifications and variations, all of which are within the scope of the inventive concept; all the details may further be replaced with technically equivalent elements.

The disclosures in Italian Patent Application no. MI2003A000696, from which this application claims priority, are incorporated herein by reference.

Claims

1. An apparatus for inserting at least one element in a first closed circuit suitable for extracorporeal substitution or support of vital functions, wherein said apparatus is characterized in that it comprises: ~ said at least one element to be inserted,

~ means suitable to constitute a second circuit that comprises said at least one element to be inserted, said means connecting said element to be inserted in said first circuit.

2. The apparatus according to claim 1, further comprising: ~ a container that contains a priming liquid;

-- means adapted to connect said element to be inserted to said container that contains a priming liquid.

3. The apparatus according to claim 1, characterized in that said means comprise a tube that is adapted to connect the element to be inserted to a container that contains a priming liquid of said first closed circuit.

4. The apparatus according to claims 2 or 3, characterized in that said means comprise a pump that is adapted to move the priming fluid.

5. The apparatus according to claim 1, further comprising:

~ means adapted to connect said element to be inserted to a container suitable to eliminate bubbles that are present.

6. The apparatus according to claim 1, further comprising means adapted to eliminate any unwanted aggregates.

7. The apparatus according to claim 1, further comprising sensors adapted to detect physical and chemical parameters.

8. The apparatus according to claim 7, wherein said parameters consist of temperature, pressure, pH, electrolytes, partial pressure of gas, and gas saturation.

9. The apparatus according to claim 7, further comprising access points adapted to accommodate said sensors.

10. The apparatus according to claim 1, wherein said at least one element to be inserted is selected from the group that consists of a oxygenation chamber, a heat exchanger, an arteriolar filter, filtration means, and bubble elimination means, a blood collection tank, means that support or substitute the blood propulsion system, manifold access systems for blood sampling for analysis, and recirculation systems.

11. The apparatus according to claim 10, wherein said means that support or substitute the blood propulsion system are selected form the group that consists of a peristaltic pump and a centrifugal pump.

12. The apparatus according to claim 1, wherein said closed circuit is selected from the group that comprises a circuit for extracorporeal circulation (ECC), a circuit for respiratory support with membrane oxygenation machine (ECMO), a circuit for emergency extracorporeal circulation support (ECLS), a circuit for extracorporeal support of the respiratory function (ECLA), a circuit for extracorporeal C0 removal (ECCOR), a circuit for emergency extracorporeal cardiopulmonary function support (ECPR), circuits for extracorporeal circulation to support and/or assist specific organs, tissues, areas, regions of the body, and circuits for locoregional extracorporeal circulation in hyperthermia, for simultaneous local administration of antiblastic drugs.

13. The apparatus according to claim 1, wherein said means suitable for connection comprise connectors.

14. The apparatus according to claim 13, characterized in that the connectors further comprise quick-coupling points that are selected from the group that consists of bayonet coupling points, coupling points having a conical cross-section, and coupling points with a tail piece.

15. The apparatus according to claims 13 and 14, characterized in that said connectors and said quick-coupling points are integrated in the element to be inserted.

16. The apparatus according to claim 13, wherein said connectors are provided so that they are independent of the lines and are ready to be inserted by the operator on the active line, or are already inserted in the active line.

17. The apparatus according to claim 16, characterized in that said connectors are already inserted in the active line.

18. The apparatus according to claim 13, characterized in that said connectors are constituted by a system with three or more ways, which is provided with a device for manual or automatic shunting of the blood flow that is adapted to allow to shunt the circulation from the active line of the first circuit to the device.

19. The apparatus according to claim 18, wherein said shunting device consists of at least one ball valve.

20. The apparatus according to claim 17, characterized in that said connectors are provided with at least one access point in a manifold or series configuration for the insertion of additional elements.

21. The apparatus according to claims 1 to 20, wherein said means comprise tubes.

22. The apparatus according to any one of claims 13 to 21, wherein at least one of said connectors optionally coupled to suitable tubes allows to drain a fluid that is present as a residue in a portion of said first circuit, said portion comprising one or more elements that are technically equivalent to the inserted elements.

23. The apparatus according to claim 22, characterized in that said fluid is blood.

24. The apparatus according to claim 1, characterized in that it further comprises optional supports for the support and optimum positioning of the components.

25. The apparatus according to claim 1, characterized in that it is made of a material that is sterile or can be sterilized at a later time.

26. The apparatus according to the preceding claims, characterized in that it is made of biocompatible materials.

27. The apparatus according to claim 26, wherein said biocompatible materials are selected from the group that consists of biocompatible plastics and plastics that are rendered biocompatible by means of surface treatments. 5

28. The apparatus according to the preceding claims, characterized in that it is made of materials that are compatible with drugs, molecules, gases or substances that are used during extracorporeal circulation.

29. The apparatus according to the preceding claims, wherein the insertion of said element is a consequence of clogging and/or wear of an 0 element that is part of the first circuit and is technically equivalent to the inserted element, or of the exceeding of the recommended utilization times of said element of the first circuit.

30. The apparatus according to the preceding claims, characterized in that it is packaged in double packages constituted by an appropriately sealed 5 outer container that is suitable to preserve the package in an environment that is not necessarily sterile, said container containing one or more already- sterile secondary packages that can be transported inside protected environments and are suitable to be opened when necessary.

31. The apparatus according to the preceding claims, provided in an 0 already primed and bubble-free condition.

32. A method for inserting at least one element in a first closed circuit suitable for extracorporeal substitution or support of vital functions, wherein said method comprises the steps of:

~ connecting to said first circuit an apparatus according to any one of 5 claims 1 to 31, said apparatus comprising said at least one element to be inserted and means adapted to constitute a second circuit, said second circuit comprising said apparatus inserted in said first active circuit,

~ diverting the flow of blood from the first closed circuit into said second circuit, optionally isolating at the same time part of the first circuit, said 0 isolated part comprising an element that is functionally identical to said at least one inserted element, wherein said steps occur during blood perfusion of said first circuit and wherein said perfusion is never halted.

33. The method according to claim 32, further comprising the step of priming said second circuit.

34. The method according to claim 32, further comprising the step of eliminating the bubbles that are present in said second circuit after diverting the flow of blood.

35. The method according to claims 33 and 34, wherein said bubble removal and priming steps occur before connecting the apparatus to said first circuit.

36. The method according to claim 33, characterized in that said priming step occurs by transferring the blood contained in the blood collection container that belongs to the first circuit.

37. The method according to claim 33, characterized in that said priming step occurs by gravity transfer of a priming liquid that is contained in a container that is not part of the first circuit.

38. The method according to claim 33, characterized in that said priming step occurs by transferring, by means of a pump, a priming liquid contained in a container that is not part of the first circuit.

39. The method according to claims 32 to 38, wherein the insertion of said element is a consequence of clogging or wear of an element that is part of the first circuit and is technically equivalent to the inserted element, or is consequent to exceeding the recommended utilization times of said equivalent element.

40. The method according to claim 32, wherein said element to be inserted consists of multiple technically equivalent elements.

41. The use of an apparatus according to claim 1 in a treatment of the pediatric type.