WO2018185464A1

WO2018185464A1 - Oxygenation system

Info

Publication number: WO2018185464A1
Application number: PCT/GB2018/050794
Authority: WO
Inventors: Stephen Turner
Original assignee: Spectrum Medical Ltd.
Priority date: 2017-04-06
Filing date: 2018-03-27
Publication date: 2018-10-11
Also published as: GB201705556D0; GB2561221A

Abstract

A pressure-isolating component for an oxygenator of an extracorporeal ventilation system has an oxygenation gas inlet for supply of oxygenation gas, an exhaust chamber, and exhaust ports permitting gas passage from the exhaust chamber to the oxygenator exterior. The pressure-isolating component comprises a pressure-relief arrangement activating at a pressure-relief threshold and is thereby configured to inhibit pressure-equalising between the exhaust chamber and the oxygenator exterior unless the pressure in the exhaust chamber exceeds the pressure-relief threshold and thereby causes the pressure-relief arrangement to activate and permit pressure- equalising between the exhaust chamber and the oxygenator exterior.

Description

Oxygenation System

Field of the Invention The present invention relates to an oxygenation system and to a method for extracorporeal blood oxygenation and carbon dioxide control. In particular, the present invention relates to a hypobaric oxygenation system and method. Systems and methods of the invention are provided to remove, and/or reduce the formation of, gaseous microemboli bubbles (GME).

Background

Extracorporeal perfusion is a process in which blood from a patient is circulated outside the patient's body, to be re-oxygenated and to have its carbon-dioxide levels adjusted, to be returned to the patient. More specifically, venous (oxygen-reduced) blood which has been removed from a patient via an incoming line, or venous line, is oxygenated by exposure to an oxygenation gas in an oxygenator for supply via an outgoing line, or arterial line, back to the patient as arterial blood. Extracorporeal perfusion is used to substitute heart and lung functionality during a medical procedure, eg open heart surgery or lung treatment. Extracorporeal blood is brought into a condition for subsequent return to the patient. Blood conditioning includes setting an appropriate temperature, flow rate, line pressure, and mixing with agents such as anti-coagulants. The oxygen content of the blood is increased in an oxygenator, where also the carbon dioxide content is adjusted. In the oxygenator, blood is exposed to an oxygenation gas via an interface through which oxygen is permitted to diffuse into, and to be taken up by, the blood. After blood has left the oxygenator, there is usually no further possibility to control the oxygen content before the blood is administered to a patient. To provide an illustration of the flow rates involved, in adult patients, blood is circulated at a typical flow rate in the region of 5 litres per minute (Ipm). For this and other reasons, many parameters must be controlled to ensure that the blood leaving the oxygenator is appropriately oxygenated and carbon dioxide levels are appropriate. International patent application PCT/GB2015/053694 by the present applicant, published as WO2016/087859, the contents of which are incorporated by reference, discloses an oxygenation system for a ventilation system comprising a flow control arrangement for controlling the flow rate of the exhaust gas relative to the oxygenation gas. WO2016/087859 also discloses a blender for preparing an oxygenation gas to be supplied to an oxygenator of a ventilation system that comprises a flow controller to control the flow rate of the oxygenation gas to the oxygenator and is capable to set the oxygen content with high accuracy at low flow rates. The blender and flow control arrangement disclosed in WO2016/087859 can be used to maintain low flow rates of an oxygenation gas while also permitting a high degree of blending accuracy and while permitting the exhaust gas to be withdrawn at an appropriate flow rate that is low, yet higher than the oxygenation gas supply.

As stated in WO2016/087859, even though vacuum may be employed to assist with a controlled exhaust gas removal at low flow rates, the gas flow within the oxygenator is achieved at atmospheric pressure, because the oxygenator housing comprises at its exhaust side openings to avoid pressurisation at the exhaust side of the oxygenator, to avoid a positive pressure gradient from exhaust side (outlet) to oxygenation gas inlet. An outlet-to-inlet pressure gradient could lead to the introduction of gross volumes of gas across the gas-blood interface (typically constituted by gas-permeable gas- exchange fibres), which in turn could lead to gas bubbles forming in the blood, which render the blood unsafe for return to a patient.

The present invention is concerned with providing additional options for blood oxygenation during extracorporeal perfusion.

Summary of the Invention

In accordance with a first aspect of the present invention, there is provided a pressure- isolating component as defined in claim 1 .

The pressure-isolating component is for an oxygenator of an extracorporeal ventilation system, wherein the oxygenator is of a type comprising an oxygenation gas inlet for supply of oxygenation gas, and an exhaust chamber, and one or more exhaust ports permitting gas passage from the exhaust chamber to an exterior of the oxygenator. The pressure-isolating component comprises a pressure-relief arrangement activating at a pressure-relief threshold, and is configured to inhibit pressure-equalising between the exhaust chamber and the oxygenator exterior unless the pressure in the exhaust chamber exceeds the pressure-relief threshold and thereby causes the pressure-relief arrangement to activate and permit pressure-equalising between the exhaust chamber and the oxygenator exterior.

Thereby, the pressure-isolating component is able to assist in maintaining sub- atmospheric pressure in the exhaust chamber, and therefore throughout the gas- exchange pathways at the gas-blood interface, unless the pressure in the exhaust chamber exceeds the pressure-relief threshold.

By "pressure-isolating", it is meant that the component is capable of maintaining a pressure differential. For instance, the pressure-isolating component is capable of maintaining sub-atmospheric pressure inside the exhaust chamber of the oxygenator, while the outside of the oxygenator, ie a clinical environment, has standard atmospheric pressure. In some embodiments, the pressure-isolating component is constituted by a housing of the oxygenator, and the housing is provided with the pressure-relief arrangement.

In such embodiments, any auxiliary exhaust ports may be provided by the same component that constitutes the pressure-relief arrangement.

In some embodiments, the pressure-relief arrangement is configured to cover one or more exhaust ports of an oxygenator, wherein, when the pressure-isolating component covers one or more exhaust ports, the pressure-isolating component is configured to inhibit pressure-equalising between the exhaust chamber and the oxygenator exterior via covered exhaust ports.

As used herein, an "exhaust chamber" is a space inside a housing of an oxygenator from where oxygenation gas can pass outside the oxygenator housing after the gas exchange at the gas-blood interface has occurred. That gas is also referred to as "exhaust gas". To provide more context, the flow path of oxygenation gas inside an oxygenator housing can be considered to follow three different zones. The first zone is a gas inlet zone in which oxygenation gas is received. From the gas inlet zone, the gas passes through the gas-blood interface, which may be regarded as a second zone. For instance, in contemporary oxygenators the gas-blood interface may be provided by a bundle of several thousand hollow fibres with porous walls (flowing blood outside the hollow fibres and oxygenation gas through the hollow fibres). The third zone is a space downstream the gas-blood interface for exhaust gas before this exits the oxygenator housing. This is because the fibre bundles do not normally extend right to the oxygenator housing, leaving a space between the densely packed fibre bundles and the oxygenator wall comprising the exhaust ports. This space that is not packed with fibres may be regarded as an exhaust chamber. At the exhaust side, an oxygenator typically comprises a main exhaust port (or exhaust line) for a continuous removal of exhaust gas, ie oxygenation gas after it has been used to change carbon dioxide levels and to oxygenate blood. The removal via the main exhaust port may be controlled, eg at a controlled flow rate, as described in international patent application PCT/GB2015/053694 by the present applicant, published as WO2016/087859.

In addition to the main exhaust port, the oxygenator housing comprises openings, also referred to as "vents", providing one or more auxiliary exhaust ports as a failsafe mechanism permitting pressure equilibration with the outside of the oxygenator, in order to prevent pressurisation in the oxygenator at the gas-blood interface if the main exhaust port or other auxiliary exhaust ports are blocked, which means that there is no escape passage for exhaust gas. Main exhaust lines may be blocked, eg, by accidentally bending a tube. If all exhaust ports are blocked but oxygenation gas continues to be supplied via the inlet, such a blockage increases the danger of gross gas volumes crossing into the blood at the gas-blood interface. The exhaust ports permit the passage of gas out of the exhaust chamber. An "auxiliary port" or "vent" may be a simple aperture, eg a slit, in the oxygenator housing without a specific connector mechanism. Oxygenators with exhaust ports are also referred to as being "porous" or "leaky", meaning that by way of multiple exhaust ports it is ensured that the exhaust chamber inside the oxygenator housing is maintained at atmospheric pressure in the event of a problem with exhaust gas removal or gas supply. Exhaust ports are positioned downstream of the gas-blood interface.

By "covering" an exhaust port, it is meant that gas exchange between the exhaust chamber and the oxygenator outside via the exhaust port is inhibited, and practically prevented. An exhaust port may be covered directly, eg by a plug. An exhaust port may be covered by a structure spanning across the exhaust port and providing a seal surrounding the exhaust port, eg by a cap. The invention may also be provided by a pressure-relief arrangement that is integral with an oxygenator housing. In that case, it may not be necessary retrofit an oxygenator housing with a pressure-relief arrangement. Instead, a housing may be designed with a pressure-relief arrangement that, in one mode of operation, is able to provide the exhaust port functionality. For instance, this could be a valve that activates when the pressure-relief threshold is exceeded in the exhaust chamber.

The provision of a pressure-isolating component of the invention enables hypobaric ventilation, which is an oxygenation procedure at sub-atmospheric pressures, while providing a fail-safe mechanism to reduce, and practically prevent, the risk of over- pressurisation in the sub-atmospheric chamber.

To set out a context for the benefits of hypobaric (sub-atmospheric) ventilation, a summary of relevant mechanisms taking place during routine atmospheric oxygenation is provided, using the example of a hollow fibre oxygenator. Oxygenation gas (ie gas that is similar to air and mixed to a required oxygen and nitrogen content in order to achieve a desired partial pressure of oxygen and partial pressure of carbon dioxide in the arterial blood) is directed via a tube and, if required, also through an anaesthetic agent vaporizer, to the gas inlet of the oxygenator, and through the bundle of hollow fibres (the gas phase), while blood is passed inside the oxygenator over the outside (the blood phase) of the hollow fibres. The fibre walls are gas-permeable and gas transfer occurs via the fibre walls due to the diffusion gradient from higher concentration (eg of oxygen in the oxygenation gas, or of carbon dioxide in the venous blood) to lower concentration (eg of oxygen in the venous blood, or of carbon dioxide in the oxygenation gas). The blood exiting the oxygenator is referred to as arterial blood and is oxygenated to have a required partial pressure of oxygen on the arterial blood (Pa02) and a required partial pressure of carbon dioxide in the arterial blood (PaC02). Pa02 and PaC02 are adjusted as follows. Pa02 can be influenced by adjusting the oxygen content of the oxygenation gas (Fraction of Inspired Oxygen, Fi02) relative to the fraction of nitrogen in the oxygenation gas (FiN2). Most of the blended air consists of nitrogen. PaC02 can be influenced by adjusting the flow rate (commonly referred to as "Sweep") of the oxygenation gas. Nitrogen in the gas phase seeks to balance itself to be equal in pressure in the gas phase compared to the blood phase.

A problem with extracorporeal oxygenation systems exists with the risk of formation of gaseous microemboli bubbles (GME) which may be propelled through the blood into the circulatory system, especially when the GME bubble has a high nitrogen content. Nitrogen-containing GME are produced when air comes into contact with blood. There are many opportunities for this to happen in a clinical scenario, eg when air and blood mix during blood suction, in open cardiac chambers, during certain drug administration procedures, during high negative pressure areas in the pump circuit, or during warming when the temperature of the blood does not allow the current volume of nitrogen to stay dissolved in solution (and nitrogen thereby "comes out of solution" in the form of bubbles).

Once in the blood stream, there often is little to no diffusion gradient between a nitrogen-containing bubble in the body and surrounding blood/tissues. Thus, a nitrogen-containing bubble, once present, tends not to dissolve into solution. GME in the blood cause proteins to stick to the bubble surfaces and relatively quickly develop a coating, which acts as a barrier further inhibiting diffusion of gases into/out of the bubble. This nitrogen-containing, protein-coated bubble then behaves much like a hollow particle with a solid surface, with the same potential morbidities associated with it as are associated with solid embolus obstruction of blood flow to the tissues. Additionally, GME can harm intimal vessel layers, leading to blood vessel inflammation. This also stimulates the coagulation pathways, which can lead to bleeding/clotting problems.

Attempts to decrease GME during extracorporeal ventilation include several techniques, such as limiting blood temperature differentials, minimizing blood suction return directly to the circuit, operating any drug injection into the blood at slow rates, flooding the operative field with C02, utilization of de-foaming chemicals in the venous/cardiotomy filters/reservoir, and arterial bubble trap/purge devices. Despite these attempts, presence of GME, as measured by sensitive instruments, is a common event in the arterial blood in extracorporeal systems.

As set out above, nitrogen is used in the oxygenation gas to set the partial pressure of oxygen in the oxygenation gas (Fi02), which, in turn, directly influences the partial pressure of oxygen in the arterial blood (Pa02) exiting the oxygenator.

By reducing or eliminating nitrogen in the oxygenation gas, eg by using pure oxygen (or a mix of oxygen and carbon dioxide), the partial pressure of nitrogen in the blood can be greatly decreased, even to the point of practical elimination. To illustrate this with an example, instead of an oxygen content similar to air, in the region of 20 to 21 % (the remaining 79 to 80% being mostly nitrogen), the oxygen content may be close to 100% (with negligible nitrogen content) in the oxygenation gas entering the inlet of the oxygenator. However, if 100% oxygen is used at atmospheric pressure for extracorporeal blood ventilation, this will result in a very high partial pressure of oxygen in the arterial blood (Pa02). A high Pa02 is undesirable because it has adverse effects on a patient, eg due to damaging free oxygen radicals that can be produced. Furthermore, high partial pressures of gases in blood have the counterproductive effect of increasing the tendency for GME development due to the dissolution-inhibiting effect. However, if higher oxygen content is provided at sub-atmospheric pressures, the corresponding partial pressure in the arterial blood leads to a lower oxygen content in the blood at equilibrium. As such, at sub-atmospheric pressure levels, a non-gas- saturated arterial blood environment is provided in the oxygenator, and the partial pressure of oxygen Pa02 is lower without the need to use nitrogen in the oxygenation gas.

Furthermore, in the non-gas-saturated condition, any bubbles in the blood tend to dissolve more quickly, practically before a protein coating can form on the bubble-blood interface. There is therefore believed to be a two-fold benefit of avoiding the need for nitrogen in the oxygenation gas and hypobaric ventilation: in addition to preventing GME formation, non-gas-saturated blood is also believed to promote the dissolution of existing bubbles.

Hypobaric oxygenation has hitherto not been used in a clinical environment because this requires providing a pressure-seal at the gas-blood interface of the oxygenator in order to be able to maintain sub-atmospheric conditions. The problem with a pressure- sealed oxygenator is that the oxygenator has no fail-safe mechanism against accidental over-pressurisation, with the associated problems set out above. A pressure-isolating component with a pressure-relief arrangement of the present invention addresses this problem by allowing an oxygenator to be pressure-isolated for a continuous sub-atmospheric oxygenation technique to be performed, while at the same time permitting the functionality of "porous", or "leaky", oxygenators to be provided, namely a fail-safe mechanism against accidental over-pressurisation in the gas phase.

As set out below, the pressure-isolating component with a pressure-relief arrangement may be integral with an oxygenator but may also be provided as a retro-fit component for existing oxygenators.

In some embodiments, the pressure-relief arrangement is dimensioned to vent at least at the flow rate of the oxygenation gas inlet.

It is understood that, even though a maximum flow rate for a specific oxygenation system may differ, the flow rate of the oxygenation gas inlet is known or can be determined. For instance, the flow rate is usually in the order of magnitude of a few litres per minute (Ipm), typically in the region of between 1 and 4 Ipm, with a typical maximum of 15 Ipm. Thus, the pressure-isolating component for a specific oxygenation system can be dimensioned to vent at least at that flow rate, eg often as high as 15 Ipm, with minimal pressure gradients. It will be understood that the maximum sweep depends on the oxygenation gas supply, but the above paragraph is intended to illustrate that a commonly chosen maximum sweep rate will be in the region of 15 Ipm. A valve may be dimensioned to vent at least at 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, or 20 Ipm. This further improves the safety of the system. By dimensioning the pressure-relief arrangement so that it is able to vent the full volume of inlet gas, pressurisation can be avoided even if the main exhaust line is blocked completely. In some embodiments, the pressure-relief arrangement comprises two or more pressure-relief units providing pressure-relief functionality, a few of the pressure-relief units combined vent at least at the flow rate capacity of the oxygenation gas inlet, or each individual ones of the pressure-relief units are dimensioned to individually vent at least at the flow rate capacity of the oxygenation gas inlet.

The pressure-relief arrangement may comprise a plurality of pressure-threshold activated pressure-relief units, such as a plurality of pressure-relief valves. In that case, dimensioning each one of the units (eg each valve) to vent at least at the flow rate of the oxygenation gas inlet ensures that each single unit (eg valve) can act as fail- safe mechanism. Likewise, a few of the plurality of pressure-relief units combined may be able to vent at the flow rate of the oxygenation gas inlet. For instance, two out of three (fewer than all) of the pressure-relief units may suffice to vent at the flow rate of the oxygenation gas inlet. This ensures that the fail-safe mechanism as able to reach the required flow capacity without all pressure-relief units activating.

Providing a plurality of fail-safe measures further increases the safety of the pressure- isolating component.

In some embodiments, the pressure-relief arrangement comprises one or more pressure-relief valves.

For instance, an above-mentioned pressure-relief unit may be constituted by a pressure-relief valve, such as a duckbill valve. The pressure-relief arrangement may be described as a positive pressure-relief mechanism, as it is intended for activation when the pressure in the exhaust chamber is above a pre-determined level (ie, "too high"). The predetermined level may be sub-atmospheric, or at a standard atmospheric pressure level. Eg, if it is intended to perform hypobaric oxygenation at around 0.5 atm, the predetermined pressure-relief level may be 1 .0 atm, to ensure the pressure-relief arrangement activates even before atmospheric pressure is reached inside an oxygenator housing. It will be understood that different valve types may be provided depending on the local ambient atmospheric pressure. This is to ensure a valve activates automatically, or passively, at the local ambient atmospheric pressure. As such, the "predetermined pressure level" may be a pressure level at which the valve is designed to activate. It will be understood that the precise pressure level may depend on the local atmospheric pressure.

Duckbill valves are an exemplary type of pressure-relief valve that can be dimensioned to activate passively, or automatically, upon a predetermined level, and therefore provide a reliable fail-safe mechanism. However, other valve types may be used.

In some embodiments, the pressure-isolating component comprises an attachment mechanism for attachment to an oxygenator via one or more oxygenator exhaust ports.

Exhaust ports can usually be expected to be provided in the form of openings in the oxygenator housing. Edges of the openings provide surface features may be used as alignment feature and/or attachment feature for engagement and/or retention of the pressure-isolating component on the oxygenator. This facilitates the installation of the pressure-isolating component on the oxygenator. In particular, this facilitates retrofitting a pressure-isolating component on existing oxygenator designs.

It will be appreciated that there are many exhaust port geometries and so the attachment mechanism may have to be designed for a specific exhaust port geometry.

As an example of an attachment mechanism, it is an option to use resilient clips, eg a clip with a resiliently deformable shaft, to engage a rim, recess or opening of an exhaust port. The attachment may include magnets.

By providing a pressure-isolating component that can be fixed to a part of the oxygenator, retro-fitting is facilitated as it is not necessary to modify an existing oxygenator. In particular, the rim of one or more exhaust port can usually be assumed to provide a suitable engagement feature for a clip arrangement.

Furthermore, the attachment mechanism may attach to only a few of the exhaust ports while providing a pressure-isolating mechanism for all relevant exhaust ports. In some embodiments, the attachment mechanism permits gas passage via the exhaust ports when the pressure-isolating mechanism is attached to the oxygenator.

This feature provides an attachment mechanism that does itself not plug an exhaust port. To illustrate this in context, the pressure-isolating component of the invention is intended to inhibit gas passage via covered exhaust ports when installed on an oxygenator, unless the pressure-relief arrangement of the pressure-isolating component is active to temporarily deactivate the pressure-isolating function. In that case, when the pressure-relief arrangement activates, this is to ensure that gas passage is permitted via the exhaust ports. The inventor appreciated that a pressure- equalising functionality between the exhaust chamber and the oxygenator exterior can be inhibited effectively even if the exhaust ports are not plugged directly. For instance, the exhaust ports may be practically covered by a cap spanning across the exhaust port, thereby pressure-isolating the exhaust chamber from the oxygenator exterior.

This practically eliminates any delay in activating a pressure-equalising function if required. Thus, when the pressure-relief arrangement activates, the exhaust ports immediately open, ie they are immediately, without requiring an additional activation procedure, able to perform their pressure-equalising function.

This further facilitates the design of pressure-relief arrangements that may vent at a full flow rate, because the configuration of the pressure-relief arrangement is not dictated by the configuration, or cross-section, of the exhaust port. For instance, the exhaust port may be an elongate slit, and the pressure-relief arrangement may be provided in the form of duckbill valves of larger cross-section than the slit.

In some embodiments, the pressure-isolating component comprises a seal arrangement to improve the seal at contact surfaces between the pressure-isolating component and the oxygenator.

The seal arrangement may be provided in the form of an obturator ring. The shape of the seal may correspond to a seating surface on an oxygenator to be provided.

It will be appreciated that there are many oxygenator geometries and so the seal arrangement may have to be designed corresponding to an individual oxygenator design. However, it is usually possible to identify a continuous surface line on an oxygenator that can provide an air-tight seating surface for the pressure-isolating component. In some embodiments, the pressure-isolating component is configured to provide a vestibule between the one or more exhaust ports and the pressure-relief arrangement.

When the pressure-isolating component is installed on the oxygenator, surfaces of the pressure-isolating component may define walls of a vestibule, or antechamber, between the inside of the pressure-isolating component and an outside wall of the oxygenator. It will be understood that the vestibule is connected to the exhaust chamber via unplugged exhaust ports and so has the same atmospheric pressure as the exhaust chamber, which may be sub-atmospheric pressure when gas passage via the exhaust ports is permitted and the pressure-relief arrangement is not activated. A vestibule provides a flow passage from one or more exhaust ports to the one or more units of the pressure-relief arrangements. For instance, this allows gas flow from any one or more of the exhaust ports to any one or more of the pressure-relief valves.

This further reduces the risk of an exhaust port or a unit of the pressure-relief arrangement adversely affecting the fail-safe functionality of the pressure-isolating component.

In some embodiments, the pressure-isolating component is configured for repeated attachment to and non-destructive detachment from an oxygenator.

For instance, the pressure-isolating component may be provided in the form of a resilient clip.

In some embodiments, the pressure-isolating component comprises an attachment- engaging feature to facilitate attachment to an oxygenator.

For instance, if the attachment is provided by one or more clips, the clips may comprise an engagement portion of reduced cross-section to facilitate engaging a recess on the oxygenator, or the clips may comprise an engagement portion of increased diameter to facilitate engaging a protrusion on the oxygenator. In some embodiments, the attachment mechanism comprises a retention feature assisting in maintaining an attachment between the pressure-isolating component and the oxygenator.

In some embodiments, the retention feature is biased into a retaining position.

For instance, if provided in the form of a resilient clip, the retention feature may be provided in the form of a resiliently biased clip, eg clip with a resiliently deformable shaft. This provides, for instance, a secure engagement that can be achieved in a single push action.

In some embodiments, the pressure-isolating component comprises an alignment feature to assist a tight seating of the pressure-isolating component on the oxygenator.

In some embodiments, the pressure-isolating component comprises an alignment feature to assist with positioning the pressure-isolating component over a plurality of exhaust ports of the oxygenator. The alignment feature may be provided by way of a surface feature. One or more of the features described herein in relation to the pressure-isolating component may provide an aligning functionality. For instance, the seal arrangement or a part thereof may also act as an alignment feature. As another example, the attachment-engaging feature or a part thereof may also act as an alignment feature.

Furthermore, the alignment feature may be provided by a symmetric configuration of a few elements of the pressure-isolating component, or of the entire pressure-isolating component. It is not necessary for the entire pressure-isolating component to be fully symmetric, but it may be display a degree of symmetry sufficient for there to be no relevant impact on the function of the pressure-isolating component depending on the orientation of the component. For instance, for an oxygenator with radially arranged exhaust ports (an example if which it is described below), it may be appropriate to provide a pressure-isolating component with radial symmetry. To set this example out in more detail, for an oxygenator with two exhaust ports the pressure-isolating device may be mountable to the oxygenator at a 0 ° orientation, or equally at a 180 ° orientation without this affecting the function of the pressure-isolating component. Likewise, for an oxygenator with three exhaust ports to be covered, the pressure-isolating device may be mountable at any one of a 0 °, 120 ° or 240° orientation. In accordance with a second aspect of the present invention, there is provided an oxygenator as defined in claim 17, comprising one or more pressure-isolating components in accordance with the first aspect.

The oxygenator comprises an oxygenation gas inlet for supply of oxygenation gas, an exhaust chamber, and further comprises a main exhaust port and one or more auxiliary exhaust ports. The main exhaust port is configured to permit removal of gas via an exhaust line, and each auxiliary exhaust port is provided to permit passage of gas and pressure equalisation with an exterior of the oxygenator. The one or more pressure- isolating components comprise and/or cover each auxiliary exhaust ports.

It is understood that the pressure-isolating component may be a separate component for attachment to an oxygenator to be provided. For instance, the pressure-isolating component may be a cap. The pressure-isolating component may be an integral part of an oxygenator. For instance, the pressure-isolating component may be constituted by an oxygenator housing without conventionally used auxiliary exhaust ports, but with a pressure-relief arrangement that is integral with the oxygenator housing. An integral pressure- isolating component may be suitable for new oxygenator designs. The pressure-relief arrangement may comprise one or more exhaust ports that are activatable to provide a pressure-equalising functionality when the pressure in the exhaust chamber exceeds the pressure-relief threshold.

Each auxiliary exhaust port is inactivated by a pressure-isolating component. Unless the pressure-relief arrangement of one pressure-isolating component is active, the exhaust gas is removed only via the main exhaust port. This may be under controlled circumstances, such as under a controlled flow rate. In particular, the pressure in the exhaust chamber is reduced to sub-atmospheric pressures. In some embodiments, the oxygenator comprises a pressure regulator upstream of the oxygenation gas inlet.

The pressure regulator may be provided in the form of a vacuum pressure regulator. Together with a pressure-isolating component at the exhaust side, this facilitates the provision of a controlled sub-atmospheric pressure between the oxygenation gas inlet and the oxygenator exhaust ports.

In some embodiments, the oxygenator comprises a pressure sensor to provide a pressure value indicative of the pressure in the exhaust chamber.

In some embodiments, the oxygenator is configured to continuously monitor the pressure and provide the pressure value. In some embodiments, the oxygenator comprises a configuration responsive to the pressure value and to adjust the pressure level in the exhaust chamber to maintain the pressure in the exhaust chamber at a pre-determined level.

The pressure regulator may be a vacuum regulator, such as a vacuum regulator valve. This allows the sub-atmospheric pressure to be controlled to a high degree of accuracy.

The pressure regulator may be responsive to a control signal. This allows a closed-loop control to be implemented so that the pressure regulator is responsive to temporary fluctuations.

In some embodiments, the oxygenator is configured to adjust one or both of the inlet gas pressure or exhaust line pressure to maintain a sub-atmospheric pressure in the exhaust chamber while minimising a pressure gradient across the oxygenator.

A minor pressure gradient will be expected from the oxygenation gas inlet to the exhaust port to the extent this is required to induce flow. Ideally, any pressure gradient from the oxygenation gas inlet to the exhaust port of the oxygenator is only so high so as to achieve the desired total gas flow through the oxygenator. As a simplification, the present specification refers to this as "reducing", or "minimising", the pressure gradient "across the oxygenator".

The expression "across the oxygenator" refers to the pressure gradient from oxygenation gas inlet to exhaust chamber, or inlet-to-outlet pressure gradient, and not to another pressure gradient. In contrast, at the gas-blood interface a pressure gradient is intended to promote blood oxygenation and gas exchange. The pressure gradient across the gas-blood interface is not considered to be a pressure gradient across the oxygenator, even though a gas-blood interface in the form of fibre bundles may extend over a large portion of an oxygenator. In practice, the inlet-to-outlet pressure differential is insignificantly low in relation the gas-blood interface pressure gradient.

A configuration allowing the inlet or exhaust pressure to be adjusted facilitates the maintaining of sub-atmospheric pressure in the exhaust chamber while minimising the pressure gradient across the oxygenator.

In some embodiments, an anaesthetic source is provided upstream the oxygenator for providing an anaesthetic agent into the oxygenation gas.

The oxygenation gas may be used as a carrier for a vaporous anaesthetic agent.

In some embodiments, the anaesthetic source is configured to provide anaesthetic agent at atmospheric pressure.

Anaesthetic agent may be supplied into the oxygenation gas with a vaporiser. Vaporisers operate under atmospheric conditions (or atmospheric pressure plus a few additional mmHg pressure). In some embodiments, the anaesthetic source is upstream of the pressure regulator.

These features facilitate the admixing of anaesthetic agent into the oxygenation gas mix. Anaesthetic vaporisers are designed for use at atmospheric pressure. Exposure of the vaporiser compartment to sub-atmospheric pressure would cause the anaesthetic agent to evaporate more quickly in direct relation to the sub-atmospheric pressure. A configuration allowing vaporisers designed for standard atmospheric pressure to be used reduces the risk of this affecting the dosage and handling of the anaesthetic delivery. In that case, after anaesthetic agent has been introduced into the oxygenation gas via the anaesthetic source (eg an anaesthetic vaporizer), the oxygenation gas is brought to the required sub-atmospheric pressure as it passes through the pressure regulator and is then available for sub-atmospheric oxygenation.

In accordance with a third aspect of the present invention, there is provided a hypobaric oxygenation method as defined in claim 26.

Embodiments of the third aspect are defined in claims 27 to 48.

The third aspect relates to methods of using embodiments of the first and second aspect in order to facilitate the provision of hypobaric oxygenation conditions and/or to maintain hypobaric oxygenation conditions over prolonged periods of time.

The invention allows hypobaric oxygenation to be provided over prolonged periods of time, eg several days, while ensuring that a fail-safe mechanism is in place when the pressure in the exhaust chamber of an oxygenator exceeds a pressure-relief threshold.

Description of the Figures

Exemplary embodiments of the invention will now be described with reference to the Figures, in which:

Figure 1 shows a schematic arrangement of an oxygenation system incorporating an exemplary embodiment of the invention;

Figure 2 shows a schematic arrangement of an oxygenator illustrating an exemplary embodiment of the invention;

Figure 3 shows an exemplary embodiment of the invention;

Figure 4 shows a schematic arrangement of a part of an oxygenator incorporating an exemplary embodiment of the invention; and Figure 5 shows steps of an exemplary method of facilitating the provision of a hypobaric atmosphere in an oxygenator in accordance with the invention. Description

Figure 1 shows, schematically, components of an oxygenation system. The oxygenation system comprises a venous line 12 provided to receive venous blood V from a patient into a venous reservoir 10. From the venous reservoir 10, the blood is drawn by a pump 13 via a main line 14 and pumped towards an oxygenator 20 in which the venous blood V is exposed to an oxygenation gas to be oxygenated and for its carbon dioxide levels to be adjusted. The oxygenated blood exits, as arterial blood A, the oxygenator 20 via an outlet line 16 from where it may be provided to a patient. Figure 1 also shows a gas blender 30 in which oxygenation gas is prepared (mixed and brought to appropriate flow conditions such as flow rate and pressure) to be provided via an oxygenation gas supply line 24 in a direction indicated by the arrow 34 into the oxygenator inlet for exposure to blood in the oxygenator. The oxygenation gas is withdrawn by use of a withdrawal system 32 (eg, vacuum-assisted suction) from the oxygenator 20 via an exhaust line 26 in the direction indicated by the arrow 36. The temperature in the oxygenator 20 is controlled by temperature-controlled water supply lines 21 leading into and out of the oxygenator 20.

The oxygenation gas supply line 24 comprises vacuum regulator valve 38 constituting a pressure regulator upstream the oxygenator 20. By way of the vacuum regulator valve 38, atmospheric pressure may be maintained upstream of the vacuum regulator valve 38 in the oxygenation gas supply line 24, and sub-atmospheric pressure may be established downstream of the vacuum regulator valve 38, and therefore in the oxygenator 20.

This allows gas to be processed at atmospheric pressures upstream of the vacuum regulator valve 38. For instance, an anaesthesia vaporiser (not shown in Figure 1 ) may be provided to release anaesthetic agent into the oxygenation gas supply. If the anaesthesia vaporiser is exposed to sub-atmospheric pressures, the anaesthesia agent would evaporate at a much higher rate, with undesirable side effects. The provision of a vacuum regulator valve 38 downstream of an anaesthesia vaporiser allows hypobaric oxygenation to be performed on systems utilising anaesthetic agent in the oxygenation gas. In the Figure 1 arrangement there is also depicted a cap 40 installed on the oxygenator 20. The cap 40 constitutes a pressure-isolating component.

Figure 2 shows in more detail a schematic drawing of the oxygenator 20 together with the cap 40. Figure 2 shows the main line 14 for supply of venous blood V into the oxygenator via a blood inlet Bl, from where blood is passed via a gas-permeable interface 25, constituting a gas-blood interface, at which the venous blood V is exposed to the oxygenation gas. In an oxygenated condition, the blood exits as arterial blood A via a blood outlet BE into the outlet line 16. The oxygenation gas enters the oxygenator 20 via the gas inlet Gl and is transported along the gas-permeable interface 25 and withdrawn via the gas exit GE. For instance, the gas-permeable interface 25 may be provided across gas-permeable walls of hollow-fibre bundles. The gas exit GE constitutes a main exhaust port via the exhaust line 26, and may be configured to permit a controlled removal (eg, removal at a controlled flow rate) of exhaust gas. The oxygenator 20 comprises a housing 22 containing the gas-permeable interface 25 (eg, densely packed hollow fibre bundles) and downstream of the gas-permeable interface 25 there is a less densely packed space constituting an exhaust chamber 1 . The housing 22 separates the exhaust chamber 1 from an oxygenator exterior 2. In addition to the main exhaust port constituted by the gas exit GE, the housing 22 comprises a plurality of openings 28 constituting auxiliary exhausts which provide a gas passage between the exhaust chamber 1 and the oxygenator exterior 2, to provide a means of pressure equilibration between the outside atmosphere and the exhaust chamber 1 . By virtue of the openings 28, the oxygenator 20 may be referred to as a 'porous', or 'leaky', oxygenator type. In particular, although indicated only schematically, in operation all ports or connections with the oxygenator 20, such as the blood inlet Bl, the blood outlet BE, the gas inlet Gl, the gas exit GE, and the water supply lines 21 , are not open to atmospheric pressures and do not permit pressure- equilibration between the oxygenator exterior 2 from the oxygenator inside. Thus, when the oxygenator is connected and in use, apart from the openings 28 there are no other gas passages across the housing 22 from the oxygenator exterior 2 to the exhaust chamber 1 .

As shown in Figure 2, the oxygenator 20 is provided with a cap 40 constituting a pressure-isolating arrangement. The cap 40 is positioned over the openings 28 and comprises a wall 44 isolating the oxygenator exterior 2 from the exhaust chamber 1 .

With the cap 20 installed on the exterior side of the housing 22, the wall 44 defines an inner space 46 inside the cap 40. The inner space 46 constitutes a vestibule. The wall 44 comprises a plurality of integral duckbill valves 42. Each duckbill valve 42 constitutes a pressure-relief unit of a pressure-relief arrangement. The duckbill valves 42 are configured as positive pressure-relief valves activating at a pressure-relief threshold. The cap 40 is attached to the oxygenator 20 in a manner that permits gas passage between the exhaust chamber 1 and the inner space 46 via the openings 28. However, gas passage between the inner space 46 and the oxygenator exterior 2 via the duckbill valves 42 is permitted only when the duckbill valves 42 open, ie when the pressure in the oxygenator chamber exceeds the pressure-relief threshold of the duckbill valves 42.

Figure 3 shows an exemplary embodiment of a cap 40. The numerals in Figure 3 correspond to numerals used in Figures 1 and 2 to facilitate comparison of similar features. The cap 40 has a round circumference with a mantle and a top surface. The mantle and top surface are part of a continuous wall 44. In the top surface, there are provided three duckbill valves 42. The duckbill valves are arranged in rotational symmetry and equi-angularly spaced apart from each other.

Figure 4 shows a cross-section of the cap 40 installed on an oxygenator 20. The numerals in Figure 4 correspond to numerals in the preceding Figures to facilitate comparison of similar features. Only a portion of the housing 22 of the oxygenator 20 is shown, namely the portion of the housing 22 approximately corresponding to the exhaust chamber 1 . The oxygenator 20 comprises a plurality of apertures 28 (only one aperture 28 is shown in Figure 4) which, in the absence of a cap 40, provides a gas passage from the exhaust chamber 1 to the oxygenator exterior 2. The cap 40 is installed on the oxygenator 20 by way of a plurality of resilient clips 52 (only one resilient clip 52 is shown in Figure 4). For instance, for an oxygenator 20 with three apertures 28, a corresponding number of resilient clips 52 may be provided. It will be understood that any number of resilient clips may be provided. The clips constitute an example of an attachment mechanism to attach the cap 40 to the oxygenator via the apertures 28. The clips are designed with a shaft diameter so that when the cap 40 is attached, gas passage via the apertures 28 is not impeded by the resilient clips 52.

The resilient clips 52 taper towards their end and thereby comprise an engaging portion of reduced cross-section to facilitate attachment. The resilient clips 52 permit repeated attachment to and non-destructive detachment from the oxygenator 20, if required. At the rim of the cap 40 there is provided an obturator ring 50 that constitutes a seal arrangement. The resilient clips 52 also constitute an alignment feature. As the resilient clips 52 are positioned on the oxygenator 20, the obturator ring 50 also is positioned in the manner intended for a secure and gas-tight seat, and pressed against the housing 22 of the oxygenator 20 to provide a tight seal. The alignment feature and the attachment feature may be constituted by different elements.

The housing 22 comprises three equi-angularly spaced apart apertures 28. Likewise, the cap 40 comprises three equi-angularly spaced apart resilient clips 52. Also, the obturator ring 50 is circular and provided against a corresponding circular contact line of the housing 22. Thereby, the cap 40 exhibits a degree of rotational symmetry meaning that the cap can be fixed to the housing in any one of three orientations (0 degrees, 120 degrees, or 240 degrees) without this affecting the pressure-isolating performance or the pressure-relief performance. The obturator ring 50 improves the seal between the cap wall 44 and the oxygenator housing 22. Thus, inside the cap 40 there is defined an inner space 46, constituting a vestibule, between the outside of the oxygenator housing 22 and the inside of the cap 40. The duckbill valves 42 are each configured to activate when the pressure inside the exhaust chamber (eg inside the inner space 46) exceeds a pressure-relief threshold. In practice, the pressure-relief threshold may be close to or at atmospheric pressure. The duckbill valves may open "passively" ie when the pressure differential between the exhaust chamber and the outside is reduced (the pressure differential being reduced because the pressure inside the exhaust chamber rises from a sub- atmospheric level to an atmospheric level).

When any one or more of the duckbill valves 42 open, gas passage is permitted along a route indicated by an arrow 54, from the exhaust chamber 1 via the aperture 28 (and any other apertures) into the inner space 46, and further from the inner space 46 via the duckbill valve 42 (and any other open valves) to the oxygenator exterior 2.

Although there is only a single aperture 28 and a single duckbill valve 42 shown in the cross-section of Figure 4, it will be understood that pressure equilibration may occur via any one or more of the apertures and/or components of the pressure-relief mechanism. In operation, the oxygenation system will continue to establish a low-pressure atmosphere in the exhaust chamber 1 . As soon as the pressure in the exhaust chamber 1 falls below the pressure-relief threshold, eg because a blockage of the exhaust line has been removed and low-pressure conditions inside the exhaust chamber 1 are restored, the duckbill valves 42 will close and the pressure-isolating functionality of the cap 40 will be restored.

Although described as a retro-fit component in Figures 1 to 4, the pressure-isolating functionality with a pressure-relief arrangement may be integral with the housing. In that case, the housing may not comprise apertures as such, but may comprise a pressure-relief mechanism providing a pressure-isolating functionality with threshold- triggered pressure-relief functionality.

Figure 5 shows steps of a method 60 of facilitating the provision of a hypobaric atmosphere in an oxygenator of an extracorporeal ventilation system. The extracorporeal ventilation system is of a type comprising an oxygenation gas inlet for supply of an oxygenation gas and an exhaust chamber with exhaust ports permitting gas to pass outside the oxygenator. The method 60 comprises the following steps:

In step 62, a pressure-isolating mechanism is provided that is suitable for allowing a sub-atmospheric pressure in the exhaust chamber to be maintained. The pressure- isolating mechanism may be provided in the form of a housing as described above, or in the form of a component to cover auxiliary exhaust ports, such as a cap described above. The method may comprise a step of installing a pressure-isolating mechanism via an exhaust port. The method may comprise a step of ensuring that gas passage through an exhaust port is not inhibited when the cap is installed.

In step 64, a pressure-relief arrangement is provided to allow pressure-equalising between the exhaust chamber and the outside of the oxygenator if a pressure-relief threshold is exceeded. The pressure-relief arrangement may be dimensioned to vent at least at the flow rate capacity of the oxygenation gas inlet. As part of the pressure- relief arrangement, two or more pressure-relief units may be provided. A few (two or more) of the pressure-relief units combined may be able to vent at least at the flow rate of the oxygenation gas inlet. Alternatively, individual pressure-relief units may be dimensioned to vent at the oxygenation gas inlet rate.

In step 66, the pressure-relief arrangement is configured to activate at a pressure-relief threshold. The configuration may be a property of the pressure-relief arrangement, such as the properties of a duckbill valve. In optional step 68, a vacuum pressure regulator is provided in the supply line upstream of the oxygenation gas inlet. In optional step 70, hypobaric oxygenation is performed by using the pressure regulator in the oxygenation gas supply line to modulate pressure. The pressure at the exhaust side may be modulated by controlling the exhaust line pressure. In optional step 72, an anaesthetic source is used to provide anaesthetic agent upstream of the pressure regulator. This allows anaesthetic agent to be provided at atmospheric pressures.

By way of the pressure-isolating mechanism, the oxygenator 20 can be pressure- isolated while providing a fail-safe mechanism against over-pressurisation.

Claims

CLAIMS:

1 . A pressure-isolating component for an oxygenator of an extracorporeal ventilation system, wherein the oxygenator is of a type comprising an oxygenation gas inlet for supply of oxygenation gas, and an exhaust chamber, and one or more exhaust ports permitting gas passage from the exhaust chamber to an exterior of the oxygenator,

wherein the pressure-isolating component comprises a pressure-relief arrangement activating at a pressure-relief threshold, and

wherein the pressure-isolating component is configured to inhibit pressure- equalising between the exhaust chamber and the oxygenator exterior unless the pressure in the exhaust chamber exceeds the pressure-relief threshold and thereby causes the pressure-relief arrangement to activate and permit pressure-equalising between the exhaust chamber and the oxygenator exterior.

2. The pressure-isolating component according to claim 1 , constituted by a housing of the oxygenator, wherein the housing is provided with the pressure-relief arrangement.

3. The pressure-isolating component according to claim 1 , configured to cover one or more exhaust ports of an oxygenator, wherein, when the pressure-isolating component covers one or more exhaust ports, the pressure-isolating component is configured to inhibit pressure-equalising between the exhaust chamber and the oxygenator exterior via covered exhaust ports.

4. The pressure-isolating component in accordance with any one of the preceding claims, wherein the pressure-relief arrangement is dimensioned to vent at least at the flow rate capacity of the oxygenation gas inlet.

5. The pressure-isolating component in accordance with any one of the preceding claims, wherein the pressure-relief arrangement comprises two or more pressure-relief units providing pressure-relief functionality, wherein a few of the pressure-relief units combined are able to vent at least at the flow rate capacity of the oxygenation gas inlet, or wherein individual ones of the pressure-relief units are dimensioned to individually vent at least at the flow rate capacity of the oxygenation gas inlet.

6. The pressure-isolating component in accordance with any one of the preceding claims, wherein the pressure-relief arrangement comprises one or more pressure-relief valves.

7. The pressure-isolating component in accordance with any one of claims 3 to 6, comprising an attachment mechanism for attachment to an oxygenator via one or more oxygenator exhaust ports.

8. The pressure-isolating component in accordance with any one of claims 3 to 7, wherein the attachment mechanism permits gas passage via the exhaust ports when the pressure-isolating mechanism is attached to the oxygenator.

9. The pressure-isolating component in accordance with any one of claims 3 to 8, comprising a seal arrangement to improve the seal at contact surfaces between the pressure-isolating component and the oxygenator.

10. The pressure-isolating component in accordance with any one of claims 3 to 9, configured to provide a vestibule between the one or more exhaust ports and the pressure-relief arrangement.

1 1 . The pressure-isolating component in accordance with any one of claims 3 to 10, configured for repeated attachment to and non-destructive detachment from an oxygenator.

12. The pressure-isolating component in accordance with any one of claims 3 to 1 1 , comprising an attachment-engaging feature to facilitate attachment to an oxygenator.

13. The pressure-isolating component in accordance with any one of claims 3 to 12, wherein the attachment mechanism comprises a retention feature assisting in maintaining an attachment between the pressure-isolating component and the oxygenator.

14. The pressure-isolating component in accordance with claim 13, wherein the retention feature is biased into a retaining position.

15. The pressure-isolating component in accordance with any one of claims 3 to 14, comprising an alignment feature to assist a tight seating of the pressure-isolating component on the oxygenator.

16. The pressure-isolating component in accordance with any one of claims 3 to 15, comprising an alignment feature to assist with positioning the pressure-isolating component over a plurality of exhaust ports of the oxygenator.

17. An oxygenator for a perfusion system, comprising one or more pressure- isolating components in accordance with any one of the preceding claims,

wherein the oxygenator comprises an oxygenation gas inlet for supply of oxygenation gas, and an exhaust chamber, and further comprises a main exhaust port and one or more auxiliary exhaust ports, wherein the main exhaust port is configured to permit removal of gas via an exhaust line, and each auxiliary exhaust port is provided to permit passage of gas and pressure equalisation with an exterior of the oxygenator, wherein the one or more pressure-isolating components comprise and/or cover the one or more auxiliary exhaust ports.

18. The oxygenator in accordance with claim 17, comprising a pressure regulator upstream of the oxygenation gas inlet.

19. The oxygenator in accordance with claim 17 or 18, comprising a pressure sensor to provide a pressure value indicative of the pressure in the exhaust chamber.

20. The oxygenator in accordance with claim 19, configured to continuously monitor the pressure and provide the pressure value.

21 . The oxygenator in accordance with claim 19 or 20, comprising a configuration responsive to the pressure value and to adjust the pressure level in the exhaust chamber to maintain the pressure in the oxygenation chamber at a pre-determined level.

22. The oxygenator in accordance with any one of claims 17 to 21 , configured to adjust one or both of the inlet gas pressure and the exhaust line pressure to maintain sub-atmospheric pressure in the oxygenation chamber while minimising a pressure gradient across the oxygenator.

23. The oxygenator in accordance with any one of claims 17 to 22, comprising or being connected to an anaesthetic source for providing an anaesthetic agent into the oxygenation gas.

24. The oxygenator in accordance with claim 24, wherein the anaesthetic source is configured to provide anaesthetic agent at atmospheric pressure.

25. The oxygenator in accordance with claim 23 or 24 when dependent on any one of claims 18 to 22, wherein the anaesthetic source is upstream of the pressure regulator.

26. A method of providing a hypobaric atmosphere in an oxygenator of an extracorporeal ventilation system, wherein the extracorporeal ventilation system is of a type comprising an oxygenation gas inlet for supply of oxygenation gas, and an exhaust chamber with exhaust ports permitting gas to pass outside the oxygenator, the method comprising:

providing a pressure-isolating mechanism suitable for allowing a sub- atmospheric pressure in the exhaust chamber to be maintained;

providing a pressure-relief arrangement on the oxygenator;

configuring the pressure-relief arrangement to activate at a pressure-relief threshold.

27. The method in accordance with claim 26, wherein providing a pressure-isolating mechanism comprises providing a pressure-isolating oxygenator housing.

28. The method in accordance with claim 26, wherein providing a pressure-isolating mechanism comprises providing a pressure-isolating component configured to cover auxiliary exhaust ports of the oxygenator housing, and covering the exhaust ports of the oxygenator housing.

29. The method in accordance with any one of claims 26 to 28, comprising dimensioning the pressure-relief arrangement to vent at least at the flow rate capacity of the oxygenation gas inlet.

30. The method in accordance with any one of claims 26 to 39, wherein providing a pressure-relief arrangement comprises providing two or more pressure-relief units providing pressure-relief functionality, wherein a few of the pressure-relief units combined are able to vent at least at the flow rate capacity of the oxygenation gas inlet, or wherein individual ones of the pressure-relief units are dimensioned to individually vent at least at the flow rate capacity of the oxygenation gas inlet.

31 . The method in accordance with any one of claims 26 to 30, wherein providing a pressure-relief arrangement comprises providing one or more pressure-relief valves.

32. The method in accordance with any one of claims 28 to 31 , wherein the pressure-isolating component comprises an attachment mechanism for attachment to an oxygenator via one or more oxygenator exhaust ports, and wherein the method comprises using the attachment mechanism to attach the pressure-isolating component to the oxygenator.

33. The method in accordance with claim 32, wherein attaching the pressure- isolating component to the oxygenator comprises ensuring a gas passage via an exhaust port is maintained.

34. The method in accordance with any one of claims 28 to 33, comprising providing a seal at contact surfaces between the pressure-isolating component and the oxygenator.

35. The method in accordance with any one of claims 28 to 34, comprising providing a vestibule between one or more exhaust ports and the pressure-relief arrangement.

36. The method in accordance with any one of claims 28 to 35, comprising providing the pressure-isolating component with an attachment-engaging feature to facilitate attachment to an oxygenator.

37. The method in accordance with any one of claims 32 to 36, comprising providing the attachment mechanism with a retention feature, wherein the retention feature is configured to assist in maintaining an attachment between the pressure- isolating component and the oxygenator.

38. The method in accordance with claim 37, wherein the retention feature is biased into a retaining position.

39. The method in accordance with any one of claims 28 to 38, comprising providing the pressure-isolating component with an alignment feature to assist a tight seating of the pressure-isolating component on the oxygenator.

40. The method in accordance with any one of claims 28 to 39, comprising providing the pressure-isolating component with an alignment feature to assist with positioning the pressure-isolating component over a plurality of exhaust ports of the oxygenator.

41 . The method in accordance with any one of claims 28 to 40, comprising providing a pressure regulator at or upstream of the oxygenation gas inlet.

42. The method in accordance with any one of claims 26 to 41 , comprising providing a pressure sensor and using the pressure sensor to obtain a pressure value indicative of the pressure in the exhaust chamber.

43. The method in accordance with claim 42, comprising continuously monitoring the pressure to provide the pressure value.

44. The method in accordance with claims 42 or 43, comprising obtaining the pressure value and adjusting, in response to the pressure value, the pressure level in the exhaust chamber to maintain the pressure in the exhaust chamber at a predetermined level.

45. The method in accordance with any one of claims 26 to 44, comprising adjusting one or both of the inlet gas pressure and the exhaust line pressure to maintain sub-atmospheric pressure in the oxygenation chamber, while minimising a pressure gradient across the oxygenator.

46. The method in accordance with any one of claims 26 to 45, comprising providing the oxygenator with an anaesthetic source for providing an anaesthetic agent into the oxygenation gas.

47. The method in accordance with claim 46, comprising configuring the anaesthetic source to provide anaesthetic agent at atmospheric pressure.

48. The method in accordance with claim 46 or 47, comprising using a pressure regulator downstream of the anaesthetic source to regulate the pressure in the oxygenator independently of the pressure at the anaesthetic inlet.