Extracorporeal blood treatment apparatus

Abstract

Extracorporeal blood treatment apparatus comprising a disposable set, the disposable set comprising: a blood circuit with a blood withdrawal line extending between a first end connected to the treatment unit and a second end, and with a blood return line extending between a first end connected to the treatment unit and a second end; a fluid infusion line with a pressure valve and extending between a first end connected to the blood circuit and a second end for connection to an infusion source, wherein the pressure valve is configured to switch from an interception position to a flow position when a differential pressure across the pressure valve exceeds an aperture pressure and from the flow position to the interception position when said differential pressure across the pressure valve falls below a closure pressure, and the closure pressure is below the aperture pressure; further wherein the apparatus comprises a blood pump, an infusion pump and a control unit configured to perform a pulsed infusion procedure.

Description

[0001] P51117PC00

[0002] Title

[0003] “Disposable set for extracorporeal blood treatment apparatus”

[0004] FIELD OF THE INVENTION

[0005] The present invention relates to a disposable set and an extracorporeal blood treatment apparatus comprising said disposable set, wherein the disposable set includes a degassing chamber having an infusion inlet. More in detail, the disposable set comprises (at least) two infusion inlets, one dedicated to a substitution fluid to be injected into the blood during an HF or HDF treatment with post-infusion, the other specifically designed for infusion downstream the blood inlet and upstream the blood outlet, for example to add a calcium concentrated solution to the extracorporeal blood. The present invention may also relate to a disposable set and an extracorporeal blood treatment apparatus comprising said disposable set, wherein the disposable set includes a pressure valve placed on an infusion line, wherein the pressure valve is closed below a certain pressure and open above a certain pressure. When the critical pressure is reached, the pressure valve opens and releases the back pressure as a jet of solution in the tubing. For example, the jet will occur in the degassing chamber or in a T-connector where the blood flows through the straight section of the T-connector and the jetting solution (e.g., Ca) is in a branch.

[0006] BACKGROUND

[0007] The kidneys fulfil many functions, including removal of water, excretion of catabolites (waste from metabolism, e.g. urea and creatinine), regulation of blood electrolyte concentration (e.g. sodium, potassium, magnesium, calcium, bicarbonates, phosphates, chlorides) and regulation of the acid / base equilibrium within the body, obtained in particular by removal of weak acids and production of ammonium salts. Due to various causes, a person's renal system may fail. In individuals who have lost the use of their kidneys, since these excretion and regulation mechanisms no longer work, the body accumulates water and metabolic waste and exhibits an excess of metabolites. To overcome renal dysfunction, resort is conventionally made to a blood treatment involving extracorporeal circulation within a blood circuit through an exchanger having a semipermeable membrane (dialyzer), in which the patient's blood is circulated on one side of the membrane and a dialysis liquid— comprising the main electrolytes of the blood in concentrations close to those in the blood of a healthy subject— is circulated on the other side. The patient is connected to the extracorporeal blood circuit through a withdrawal (arterial) line and a return (venous) line, wherein the withdrawal and return lines have respective needles at end portions to be connected to the vascular system of the patient.

[0008] A pressure difference is created between the two compartments of the dialyzer delimited by the semipermeable membrane, so that a fraction of plasma fluid passes, e.g. by ultrafiltration, through the membrane into the compartment containing the dialysis liquid. Blood treatment in a dialyzer as regards metabolic waste and electrolytes results from two mechanisms of molecular transport through the membrane between blood and dialysis fluid.P51117PC00

[0009] One type of kidney failure therapy is Hemodialysis ("HD”), which in general uses diffusion to remove waste products from, and restore essential substances in, a patient's blood. In HD, dialysis fluid flows on one side of a semi-permeable membrane and the patient's blood flows on the other side, so a diffusive concentration gradient occurs along the membrane between the two fluids. HD fluids are typically created by dialysis machines by mixing concentrates and clean water.

[0010] Hemofiltration ("HF”) is an alternative renal replacement therapy. HF is accomplished by pulling more plasma water from the patient than what is needed to restore fluid balance; by that, convection is used to remove toxins. Fluid balance is restored by adding so-called substitution or replacement fluid to the extracorporeal circuit during treatment. HF is particularly beneficial in removing middle and large molecules.

[0011] Hemodiafiltration (“HDF”) is a treatment modality that combines convective and diffusive transport mechanism principles.

[0012] As previously mentioned, dialysis fluid may be prepared upstream of the dialyzer by mixing pure water with a plurality of predetermined substances, such as electrolytes and buffer, to be exchanged within the dialyzer with the patient's blood. Water comes from an online port receiving purified and de-ionized tap water (e.g., by reverse osmosis), to be subsequently further filtered within the apparatus so that a substantially endless water source is provided to the blood treatment apparatus for mixing with concentrates. Alternatively, dialysis fluid is preprepared and housed in respective bags to feed the dialysis apparatus, e.g. in acute dialysis treatments. Treatment apparatuses configured to deliver extracorporeal blood treatments such as ultrafiltration, hemodialysis, hemofiltration, hemodiafiltration or plasmapheresis, or hemoperfusion or blood oxygenation / CO2 removal generally comprise an infusion line connected to the blood circuit of the disposable set: the infusion line may be used for infusing replacement fluid into the extracorporeal blood and / or to infuse one or more specific substances to control blood parameters.

[0013] Furthermore, an anticoagulant solution, such as citrate, may be infused in the blood circuit to avoid blood coagulation: a bag containing citrate or other regional anticoagulant is usually connected to the blood circuit upstream the filtration unit. Citrate ions, added to blood in the extracorporeal circuit before the artificial kidney, act as anticoagulants thanks to their ability to chelate calcium ions. During dialysis, part of citrate ions (including those chelated with blood calcium) passes through the filtration unit. This appreciable calcium loss is compensated by a post-filter or systemic calcium infusion. Citrate ions act as anticoagulants only in the extracorporeal circuit since, when they enter the patient's systemic circulation, they are rapidly metabolized into bicarbonate ions; thus, the risk of bleeding complications due to systemic anticoagulation is avoided.

[0014] However, to reestablish correct hemostasis, blood ion balance has to be restored— especially by adding calcium ions to the blood— at the outlet of the filter. Accordingly, as shown in PCT / EP00 / 03583, the venous line may include, beyond the bubble trap, a channel connected to a container containing a solution for reestablishing blood ion balance, namely a calcium solution. This channel is attached downstream from the bubble trap, i.e. downstream in the sense of blood circulation in the venous line before blood is returned to the patient.

[0015] The reestablishing solution has to be properly mixed with blood to homogenize the blood returned to the patient; however, a recurrent problem related to mixing has been observed: mixing does not occur uniformly and localP51117PC00

[0016] coagulation problems arise, evident especially from coagulation filaments. Therefore, there is a need to reduce local coagulation while guaranteeing proper mixing. At the same time, the extracorporeal blood treatment apparatus should guarantee proper alert and / or reaction in case of air or air bubble infusion.

[0017] EP1349632 discloses a valve mechanism on an infusion / substitution line that is kept closed and only opened when upstream pressure exceeds downstream pressure, so as to prevent retrograde flow / contamination (blood products backing up) toward the sterile fluid source.

[0018] EP 4393529 discloses an extracorporeal blood treatment disposable set / apparatus in which an infusion line is connected both to the blood withdrawal line and to the blood return (venous) line, and can be configured to form a closed-loop recirculation circuit including the filtration unit and part of the infusion line. Thus, infusion connectivity to the venous return is used primarily to support controlled recirculation / anti-stagnation conditions rather than to address localized mixing of an infused substance in the venous return.

[0019] US 2020 / 0179588 describes an extracorporeal blood treatment apparatus where a post-infusion line is connected to the blood return line upstream of a heating zone (blood warmer), together with an air trapping device on the blood return line, and optional bypass arrangements for priming and flow routing. The document teaches infusion into the venous return line in association with thermal management / priming and air handling, rather than specific structures dedicated to improved mixing of a substance (e.g., calcium) in the venous return before return to the patient.

[0020] OBJECTIVE OF THE INVENTION

[0021] The objective of this invention is therefore to at least partially solve one or more of the drawbacks described above.

[0022] A first aim is to provide a disposable set able to ensure that the infusion fluid is effectively mixed with the blood before it returns to the patient.

[0023] A further goal is to provide a disposable set able to allow the apparatus to prevent or minimize local blood coagulation in the extracorporeal blood circuit.

[0024] A further goal is to provide a disposable set able to optimize the fluid dynamics and ensuring thorough mixing and interaction of the infusion fluid with the blood, thereby enhancing the effectiveness of the treatment by ensuring homogeneous fluid properties before the blood is returned to the patient.

[0025] A further aim is to provide a disposable set able to properly mix a calcium solution with blood for reestablishing blood ion balance, avoiding at the same time local blood coagulation.

[0026] A further objective is to provide a cost-effective disposable set able to properly mix an infusion fluid with blood, simplify the overall design of the blood circuit leading to a reduction in the number of connections and potential leak points, enhancing the reliability and maintenance ease of the system.

[0027] Another goal is to help remove gas bubbles more effectively while infusing treatment fluids, and to detect and prevent air bubbles from reaching the patient.

[0028] At least one of the above objectives is achieved by the present invention.P51117PC00

[0029] These objects and more, which will appear more from the following description, are substantially achieved by a disposable set and an apparatus and optionally by a method in accordance with one or more of the following claims and / or aspects.

[0030] SUMMARY SECTION

[0031] A 1staspect is directed to a disposable set (100) for an extracorporeal blood treatment apparatus (1), the disposable set (100) comprising:

[0032] a treatment unit (101);

[0033] a blood circuit (17) comprising:

[0034] o a blood withdrawal line (6) extending between a first end (6a) connected to the treatment unit (101) and a second end (6b) for connection to a patient,

[0035] o a blood return line (7) extending between a first end (7a) connected to the treatment unit (101) and a second end (7b) for connection to the patient;

[0036] a fluid infusion line (74) extending between a first end (74a) connected to the blood circuit (17) and a second end (74b) for connection to an infusion substance source (11),

[0037] a degassing chamber (80) arranged on the blood return line (7) between the first end (7a) and the second end (7b) of the blood return line (7), said degassing chamber (80) comprising:

[0038] o a blood inlet (81) for blood entry;

[0039] o a blood outlet (82) for blood output;

[0040] o a fluid infusion inlet (83) connected to the first end (74a) of the fluid infusion line (74); wherein said fluid infusion inlet (83) of the degassing chamber (80) is interposed between said blood inlet (81) and said blood outlet (82) of the degassing chamber (80).

[0041] A 2ndaspect is directed to a disposable set for an extracorporeal blood treatment apparatus (1), the disposable set (100) comprising:

[0042] a treatment unit (101);

[0043] a blood circuit (17) comprising:

[0044] o a blood withdrawal line (6) extending between a first end (6a) connected to the treatment unit (101) and a second end (6b) for connection to a patient,

[0045] o a blood return line (7) extending between a first end (7a) connected to the treatment unit (101) and a second end (7b) for connection to the patient;

[0046] a fluid infusion line (74) extending between a first end (74a) connected to the blood circuit (17) and a second end (74b) for connection to an infusion substance source (11),

[0047] an auxiliary fluid infusion line (63) extending between a first end (63a) connected to the blood circuit (17), and a second end (63b) for connection to an auxiliary infusion substance source (64),

[0048] a degassing chamber (80) arranged on the blood return line (7) between the first end (7a) and the second end (7b) of the blood return line (7), said degassing chamber (80) comprising:P51117PC00

[0049] o a blood inlet (81) for blood entry;

[0050] o a blood outlet (82) for blood output;

[0051] o a fluid infusion inlet (83) connected to the first end (74a) of the fluid infusion line (74); o an auxiliary fluid infusion inlet (91) connected to the first end (63a) of the auxiliary fluid infusion line (63).

[0052] In a 2ndbis aspect according to the preceding aspect, said fluid infusion inlet (83) of the degassing chamber (80) is interposed between said blood inlet (81) and said blood outlet (82) of the degassing chamber (80). In a 3rdaspect according to any one of the preceding aspects, said blood return line (7) extends along a first tract (7') between said first end (7a) and a third end (7c) connected to the blood inlet (81) of the degassing chamber (80).

[0053] In a 4thaspect according to any one of the preceding aspects, the blood return line (7) extends along a second tract (7”) between a fourth end (7d), connected to the blood outlet (82) of the degassing chamber (80), and said second end (7b) for connection to the patient.

[0054] In a 5thaspect according to any one of the two preceding aspects, the blood return line (7) is configured to allow blood to flow from said first tract (7') of the blood return line (7) to the degassing chamber (80) and from the degassing chamber (80) to said second tract (7”) of the blood return line (7).

[0055] In a 6thaspect according to any one of the preceding aspects, the degassing chamber (80) extends, at least during an operative condition of the degassing chamber (80), along a height direction (H) from a bottom portion (84) to a top portion (85).

[0056] In a 7thaspect according to the preceding aspect, said fluid infusion inlet (83) of the degassing chamber (80) is interposed between said blood inlet (81) and said blood outlet (82) of the degassing chamber (80) with respect to said height direction (H).

[0057] In an 8thaspect according to any one of the preceding aspects in combination with aspect 6, the degassing chamber (80) has a height measured along said height direction (H), in particular wherein said height defines a main dimension of the degassing chamber (80).

[0058] In a 9thaspect according to the preceding aspect, said blood inlet (81), said blood outlet (82) and said fluid infusion inlet (83) are arranged below a midline of said height.

[0059] In a 10thaspect according to any one of the preceding aspects in combination with aspect 6, said height direction (H) is parallel, during an operative condition of said degassing chamber (80), to the gravitational force.

[0060] In a 11thaspect according to any one of the preceding aspects, the blood outlet (82) of the degassing chamber (80) defines a blood outlet direction (82a), and wherein the fluid infusion inlet (83) defines a respective infusion access direction (83a), wherein the infusion access direction (83a) is transverse, and optionally orthogonal, to the blood outlet direction (82a).

[0061] In a 12thaspect according to the preceding aspect, the infusion access direction (83a) intersects the blood outlet direction (82a).

[0062] In a 13thaspect according to any one of the preceding aspects in combination with aspect 11, the blood outlet direction (82a) is parallel to the height direction (H) of the degassing chamber.P51117PC00

[0063] In a 14thaspect according to any one of the preceding aspects in combination with aspect 11, the blood outlet direction (82a) is parallel to the gravitational force.

[0064] In a 15thaspect according to any one of the preceding aspects in combination with aspect 11, the blood inlet (81) of the degassing chamber (80) defines a respective blood inlet access direction (81a), and wherein the fluid infusion access direction (83a) is substantially parallel to the blood inlet access direction (81a).

[0065] In a 16thaspect according to the preceding aspect, the blood inlet access direction (81a) is transversal, optionally orthogonal, to the blood outlet direction (82a).

[0066] In a 17thaspect according to any one of the preceding aspects in combination with aspect 15, the blood inlet access direction (81a) is offset with respect to the blood outlet direction (82a), in particular by a distance comprised between 12 mm and 28 mm, more in particular between 15 mm and 22 mm, more in particular by a distance of 19 mm ± 1 mm.

[0067] In a 18thaspect according to any one of the preceding aspects in combination with aspect 15, the blood inlet access direction (81a) of the blood inlet (81) is transverse, optionally orthogonal, to the height direction (H) of extension of the degassing chamber (80).

[0068] In a 19thaspect according to any one of the preceding aspects, the degassing chamber (80) comprises an inner volume (86) configured to house blood and / or fluid.

[0069] In a 20thaspect according to the preceding aspect, the blood inlet (81) of the degassing chamber (80) is tangential to said inner volume (86) of the degassing chamber (80).

[0070] In a 21staspect according to any one of the two preceding aspects in combination with aspect 15, the blood inlet access direction (81a) of the blood inlet (81) of the degassing chamber (80) is tangential to said inner volume (86) of the degassing chamber (80).

[0071] In a 21stbis aspect according to any one of the preceding aspects, no venous filter is provided in an inner volume (86) of the degassing chamber (80) downstream of the blood inlet (81).

[0072] In a 22ndaspect according to any one of the preceding aspects, the blood outlet (82) and the fluid infusion inlet (83) of the degassing chamber (80) define a solid body, in particular being integral to each other.

[0073] In a 23rdaspect according to any one of the preceding aspects, the blood inlet (81), the blood outlet (82), and the fluid infusion inlet (83) of the degassing chamber (80) are made in one-piece.

[0074] In a 24thaspect according to any one of the preceding aspects in combination with aspect 19, said inner volume (86) of the degassing chamber (80) has a circular cross-sectional shape orthogonal to the height direction (H) of the degassing chamber (80).

[0075] In a 25thaspect according to any one of the preceding aspects in combination with aspect 19, the inner volume (86) of the degassing chamber fluidly connects the blood inlet (81) to the blood outlet (82).

[0076] In a 26thaspect according to any one of the preceding aspects in combination with aspect 19, said inner volume (86) comprises a main housing (87), a mixing chamber (89) and a reduced passage (88) interposed between the main housing (87) and the mixing chamber (89) so that blood is allowed to flow, during an operative condition of the disposable set, from the main housing (87), through the reduced passage (88), to the mixing chamber (89).P51117PC00

[0077] In a 27thaspect according to the preceding aspect, the fluid infusion inlet (83) comprises a nozzle (90) flowing into said mixing chamber (89), in particular wherein said nozzle (90) of the fluid infusion inlet (83) is configured to deliver infusion fluid directly into said mixing chamber (89).

[0078] In a 28thaspect according to any one of the preceding aspects in combination with aspect 26, a passage section for blood and / or fluid flow of the inner volume (86) of the degassing chamber decreases from the main housing (87) to the reduced passage (88), and then increases from the reduced passage (88) to the mixing chamber (89).

[0079] In a 29thaspect according to any one of the preceding aspects in combination with aspect 26, the reduced passage (88) defines a Venturi channel for the blood and / or fluid flowing from the main housing (87) to the mixing chamber (89).

[0080] In a 30thaspect according to any one of the preceding aspects in combination with aspect 28, said passage section of the inner volume (86) measured at said reduced passage (88) is smaller than the passage section of said inner volume (86) measured at the mixing chamber (89).

[0081] In a 31staspect according to any one of the preceding aspects in combination with aspect 28, said passage section of the inner volume (86) increases from the reduced passage (88) to the mixing chamber (89) by at least 30%, optionally at least 50% along a direction from the reduced passage (88) to the mixing chamber (89). In a 32ndaspect according to any one of the preceding aspects in combination with aspect 28, said passage section of the inner volume (86) increases along a blood path from the reduced passage (88) to the mixing chamber (89) by a rate greater than 5 mm2 / mm.

[0082] In a 33rdaspect according to any one of the preceding aspects in combination with aspect 28, the passage section of said inner volume (86) is minimum at said reduced passage (88).

[0083] In a 34thaspect according to any one of the preceding aspects in combination with aspect 28, the passage section of said inner volume (86) measured at said reduced passage (88) is comprised between 0,7 mm2and 4 mm2, optionally between 1 mm2and 3,5 mm2, more optionally between 1,6 mm2and 2,7 mm2.

[0084] In a 35thaspect according to any one of the preceding aspects in combination with aspect 26, the fluid infusion inlet (83) defines a respective infusion access direction (83a), and wherein the reduced passage (88) defines a reduced passage axis (RPA), wherein said infusion access direction (83a) is transversal, optionally orthogonal, to said reduced passage axis (RPA).

[0085] In a 36thaspect according to the preceding aspect and / or according to aspect 11, the infusion access direction (83a) is representative of a flow direction of the infusion fluid into the mixing chamber.

[0086] In a 37thaspect according to any one of the preceding aspects in combination with aspect 35, the reduced passage axis (RPA) of the reduced passage (88) is representative of a flow direction of the blood and / or fluid from the main housing (87) to the mixing chamber (89).

[0087] In a 38thaspect according to any one of the preceding aspects in combination with aspect 35, the reduced passage axis (RPA) is parallel to the height direction (H) of the degassing chamber.

[0088] In a 39thaspect according to any one of the preceding aspects in combination with aspect 35, the reduced passage axis (RPA) is parallel, and optionally coincident, to the blood outlet direction (82a).P51117PC00

[0089] In a 40thaspect according to any one of the preceding aspects in combination with aspect 26, the main housing (87), the mixing chamber (89) and the reduced passage (88) define together a solid body.

[0090] In a 41staspect according to any one of the preceding aspects in combination with aspect 26, the main housing (87), the mixing chamber (89) and the reduced passage (88) are integral to each other.

[0091] In a 42ndaspect according to any one of the preceding aspects in combination with aspect 26, the main housing (87), the mixing chamber (89) and the reduced passage (88) are made in one-piece.

[0092] In a 43rdaspect according to any one of the preceding aspects in combination with aspect 26, the main housing (87), the mixing chamber (89) and the reduced passage (88) are integrally formed I seamlessly joined together. In a 44thaspect according to any one of the preceding aspects in combination with aspect 26, the reduced passage (88) has a reduced passage section for the blood flow, and wherein the reduced passage (88) extends, along a direction orthogonal to said reduced passage section, by a length comprised between 0,5 mm and 10 mm, optionally between 0,7 mm and 5 mm, more optionally between 1 mm and 2 mm.

[0093] In a 45thaspect according to any one of the preceding aspects in combination with aspect 26, the mixing chamber (89) is at a distance from the main housing (87) of the degassing chamber (80) comprised between 0,5 mm and 10 mm, in particular between 0,7 mm and 5 mm, more optionally between 1 mm and 2 mm. In a 46thaspect according to any one of the preceding aspects, the blood inlet (81) is at a distance from the fluid infusion inlet (83) of the degassing chamber (80) comprised between 6 mm and 20 mm, in particular said distance being measured parallel to the height direction (H) of the degassing chamber (80).

[0094] In a 47thaspect according to any one of the preceding aspects in combination with aspect 26, the blood inlet (81) enters the main housing (87) at a blood inlet delivery spot (81b).

[0095] In a 48thaspect according to any one of the preceding aspects in combination with aspect 26, the fluid infusion inlet (83) enters the mixing chamber (89) at an infusion inlet delivery spot (83b) for delivering fluid in the mixing chamber (89).

[0096] In a 49thaspect according to the two preceding aspects, the blood inlet delivery spot (81b) is spaced from the infusion inlet delivery spot (83b) by a distance comprised between 12 mm and 28 mm, more in particular between 15 mm and 22 mm, more in particular by a distance of 18 mm ± 1 mm.

[0097] In a 50thaspect according to any one of the preceding aspects in combination with aspect 26, the mixing chamber (89) is interposed between the reduced passage (88) and the blood outlet (82).

[0098] In a 51staspect according to any one of the preceding aspects in combination with aspect 26, said main housing (87) comprises a conical bottom portion (87a) interposed between the blood outlet (82) and the blood inlet (81), in particular along the height direction (H) of the degassing chamber (80), so that blood is allowed to flow from the blood inlet (81), through said conical bottom portion, and towards the blood outlet (82).

[0099] In a 52ndaspect according to the preceding aspect, said conical bottom portion (87a) is interposed between the blood inlet (81) and the fluid infusion inlet (83) in particular along the height direction (H) of the degassing chamber (80).

[0100] In a 53rdaspect according to any one of the preceding aspects in combination with aspect 19 and 51, said inner volume (86) of the degassing chamber (80) includes said conical bottom portion (87a).P51117PC00

[0101] In a 54thaspect according to any one of the preceding aspects in combination with aspect 51, said conical bottom portion (87a) is upstream with respect to the mixing chamber.

[0102] In a 55thaspect according to any one of the preceding aspects in combination with aspect 51, said conical bottom portion (87a) is upstream with respect to the reduced passage.

[0103] In a 56thaspect according to any one of the preceding aspects in combination with aspect 26 and 51 , the mixing chamber (89) is interposed between said conical bottom portion (87a) and the blood outlet (82), in particular between the reduced passage (88) and the blood outlet (82).

[0104] In a 57thaspect according to any one of the preceding aspects, the disposable set comprises said infusion substance source (11) fluidly connected to the second end (74b) of the fluid infusion line (74), said infusion substance source (11) being a calcium solution source or a calcium solution bag containing or configured to contain a calcium solution fluid.

[0105] In a 58thaspect according to any one of the preceding aspects, at least the first end (74a) of the fluid infusion line (74) comprises an inner lumen and an external surface, wherein the fluid infusion line (74) is received inside the fluid infusion inlet, wherein the external surface of the fluid infusion line (74) contacts, at the first end (74a) of the fluid infusion line (74), an inner surface of the fluid infusion inlet (83).

[0106] In a 59thaspect according to any one of the preceding aspects, the fluid infusion inlet (83) comprises a stop portion (83c) facing, and in particular contacting, a thickness wall of the first end (74a) of the fluid infusion line (74), said stop portion (83c) being substantially orthogonal to the infusion access direction (83a).

[0107] In a 60thaspect according to the preceding aspect, said thickness wall of the fluid infusion line (74) defines the thickness of the fluid infusion line (74) between the inner lumen and the external surface of the fluid infusion line (74).

[0108] In a 61staspect according to any one of the preceding aspects, an end, in particular the third end (7c), of the blood return line (7) is received inside the blood inlet (81).

[0109] In a 62ndaspect according to any one of the preceding aspects, an external surface of the blood return line (7) contacts, in particular at said third end (7c) of the blood return line (7), an inner surface of the blood inlet (81). In a 63rdaspect according to any one of the preceding aspects, the blood inlet (81) comprises a stop portion (81c) facing, and in particular contacting, a thickness wall of an end (7c) of the blood return line (7), said stop portion (81c) being substantially orthogonal to the blood inlet access direction (81a).

[0110] In a 64thaspect according to any one of the preceding aspects, said thickness wall of the blood return line (7) defines a thickness of the blood return line (7) measured between an inner lumen and an external surface of the blood return line (7).

[0111] In a 65thaspect according to any one of the preceding aspects, an end, in particular the fourth end (7d), of the blood return line (7) is received inside the blood outlet (82).

[0112] In a 66thaspect according to any one of the preceding aspects, an external surface of the blood return line (7) contacts, in particular at said fourth end (7d) of the blood return line (7), an inner surface of the blood outletP51117PC00

[0113] In a 67thaspect according to any one of the preceding aspects, the blood outlet (82) comprises a stop portion (82c) facing, and in particular contacting, a thickness wall of an end (7d) of the blood return line (7), said stop portion (82c) of the blood outlet (82) being substantially orthogonal to the blood outlet direction (82a) e.g., access direction.

[0114] In a 68thaspect according to any one of the preceding aspects, said thickness wall of the blood return line (7) defines a thickness of the blood return line (7) measured between an inner lumen and an external surface of the blood return line (7).

[0115] In a 69thaspect according to any one of the preceding aspects in combination with aspect 27, the nozzle (90) of the fluid infusion inlet (83) has a fluid passage section that decreases in size in the direction of the fluid infusion, optionally said direction of the fluid infusion being directed from the first end (74a) of the fluid infusion line (74) towards the mixing chamber (89) of the degassing chamber (80).

[0116] In a 70thaspect according to any one of the preceding aspects in combination with aspect 27, said nozzle has tronco-conical shape.

[0117] In a 71staspect according to any one of the preceding aspects, the degassing chamber (80) comprises an auxiliary fluid infusion inlet (91), distinct from the fluid infusion inlet (83),

[0118] and wherein disposable set comprises an auxiliary fluid infusion line (63) extending between a first end (63a), connected to the auxiliary fluid infusion inlet (91), and a second end (63b) for connection to an auxiliary infusion substance source (64).

[0119] In a 72ndaspect according to the preceding aspect, said blood inlet (81) is interposed between the fluid infusion inlet (83) and the auxiliary fluid infusion inlet (91) along the height direction (H) of the degassing chamber (80). In a 73rdaspect according to any one of the preceding aspects in combination with aspect 71, the auxiliary infusion substance source (64) comprises a fluid bag containing or configured for containing dialysis fluid or a replacement fluid.

[0120] In a 74thaspect according to any one of the preceding aspects in combination with aspect 71, the auxiliary infusion substance source (64) is different from the infusion substance source (11).

[0121] In a 75thaspect according to any one of the preceding aspects in combination with aspect 71, the substance contained in the auxiliary infusion substance source (64) is different from the substance contained in the infusion substance source (11).

[0122] In a 76thaspect according to any one of the preceding aspects, the degassing chamber (80) has a height measured along said height direction (H), in particular wherein said height defines the main dimension of the degassing chamber (80).

[0123] In a 77thaspect according to the preceding aspect, said auxiliary fluid infusion inlet (91) is arranged above a midline of said height.

[0124] In a 78thaspect according to any one of the preceding aspects, the auxiliary fluid infusion inlet (91) defines an auxiliary infusion access direction (91a).

[0125] In a 79thaspect according to the preceding aspect, the auxiliary infusion access direction (91a) is transverse, and optionally orthogonal, to the blood outlet direction (82a).P51117PC00

[0126] In an 80thaspect according to any one of the preceding aspects in combination with aspect 78, the auxiliary infusion access direction (91a) intersects the blood outlet direction (82a).

[0127] In an 81staspect according to any one of the preceding aspects in combination with aspect 78, the auxiliary infusion access direction (91a) is transverse, optionally orthogonal, to the height direction of extension of the degassing chamber (80).

[0128] In an 82ndaspect according to any one of the preceding aspects in combination with aspect 78, the auxiliary infusion access direction (91a) of the auxiliary fluid infusion inlet (91) is orthogonal to the infusion access direction (83a) of the fluid infusion inlet (83).

[0129] In an 83rdaspect according to any one of the preceding aspects in combination with aspect 78, the auxiliary infusion access direction (91a) of the auxiliary fluid infusion inlet (91) is orthogonal to the blood inlet access direction (81a) of the blood inlet (81).

[0130] In an 84thaspect according to any one of the preceding aspects, the degassing chamber (80) comprises a first body (80a) and a second body (80b) coupled to each other defining the degassing chamber (80) in one piece. In an 85thaspect according to the preceding aspect, the first body (80a) is made in one piece by plastic molding and wherein the second body (80b) is made, separately by the first body (80a), in one piece by plastic molding. In an 86thaspect according to any one of the preceding aspects in combination with aspect 84, the first body (80a) includes the blood inlet (81), the blood outlet (82) and the fluid infusion inlet (83).

[0131] In an 87thaspect according to any one of the preceding aspects in combination with aspect 84, the second body (80b) includes the auxiliary fluid infusion inlet (91).

[0132] In an 88thaspect according to any one of the preceding aspects in combination with aspect 84, the first body (80a) is heat-sealed to the second body (80b) or wherein the first body (80a) is glued to the second body (80b). In an 89thaspect according to any one of the preceding aspects in combination with aspect 84, the first body (80a) is arranged below to the second body (80b) along the height direction (H) of the degassing chamber (80). In a 90thaspect according to any one of the preceding aspects, the degassing chamber comprises a top aperture (92) connected to a service line (93), said service line (93) extending between a first end (93a) fluidly connected to said top aperture (92) of the degassing chamber (80) and a second end (93b).

[0133] In a 91staspect according to the preceding aspect, said second end (93b) of the service line (93) is configured to be connected to a level controlling system (93c) of the extracorporeal blood treatment apparatus (1) configured to control and / or vary a fluid level in the degassing chamber (80), in particular wherein the fluid level is a level of the blood or a level of a mixture of blood and fluid or a level of a fluid.

[0134] In a 92ndaspect according to any one of the preceding aspects in combination with aspect 90, said service line (93) comprises an access site configured to allow an operator for manually drawing fluid, in particular blood and / or air and / or fluid, from said service line (93) or for manually sending fluid, in particular air, into said service line (93).

[0135] In a 93rdaspect according to any one of the preceding aspects in combination with aspect 90, said service line (93) or said top aperture (92) of the degassing chamber (80) comprises a hydrophobic membrane configured to allow passage of gas and to prevent passage of liquid.P51117PC00

[0136] In a 94thaspect according to any one of the preceding aspects in combination with aspect 90, said top aperture (92) of the degassing chamber (80) is arranged on a top portion of the degassing chamber (80) in particular said top portion of the degassing chamber being defined in an operative condition of the degassing chamber. In a 95thaspect according to any one of the preceding aspects in combination with aspect 71, the auxiliary fluid infusion inlet (91) is interposed between said top aperture (92) and said blood inlet (81) along the height direction.

[0137] In a 96thaspect according to any one of the preceding aspects, the fluid infusion line (74) includes a respective pump tract (74p) configured to be engaged by an infusion pump (75) of the extracorporeal blood treatment apparatus (1), wherein said infusion pump (75) is configured to determine a fluid flow, at least during an operating condition, from the infusion substance source (11) to the fluid infusion inlet (83) of the degassing chamber (80).

[0138] In a 97thaspect according to any one of the preceding aspects in combination with aspect 2 or 71, the auxiliary fluid infusion line (63) includes a respective pump tract (63p) configured to be engaged by an auxiliary infusion pump (65) of the extracorporeal blood treatment apparatus (1) which is configured to determine a fluid flow, at least during an operating condition, from the auxiliary infusion substance source (64) to the degassing chamber (80), optionally to the auxiliary fluid infusion inlet (91) of the degassing chamber (80).

[0139] In a 98thaspect according to any one of the preceding aspects in combination with aspect 90, the treatment unit (101) comprises one or more of a filtration unit (2) and a gas exchanger.

[0140] In a 99thaspect according to the preceding aspects, the filtration unit (2) is a filter for hemodialysis and / or blood ultrafiltration.

[0141] In a 100thaspect according to any one of the preceding aspects, the blood withdrawal line (6) includes a blood pump tract (6p) configured to be engaged by a blood pump (21) of the extracorporeal blood treatment apparatus (1) which is configured to determine a blood flow at least during an operating condition, said blood flow in the blood circuit (17) being in a direction from the blood withdrawal line (6) towards the treatment unit (101) and from the treatment unit (101) through the blood return line (7).

[0142] In a 101staspect according to the preceding aspect, the disposable set (100) comprises a pre-infusion line (51) extending between a first end (51a) connected to the blood withdrawal line (6), upstream the blood pump tract (6p), and a second end (51b) for connection to a pre-infusion substance source (10).

[0143] In a 102ndaspect according to the preceding aspect, said pre-infusion substance source (10) comprises an infusion bag housing a fluid infusion solution, in particular said infusion solution comprising one of a replacement fluid, saline, and a regional anticoagulant solution, optionally said infusion solution comprising one or more components between bicarbonate, acetate, lactate, citrate, and electrolytes.

[0144] In a 103rdaspect according to any one of the preceding aspects in combination with aspect 101, the first end (51a) of the pre-infusion line (51) is upstream the blood pump tract (6p).

[0145] In a 104thaspect according to any one of the preceding aspects in combination with aspect 100, the blood pump tract (6p) is interposed between the treatment unit (101) and the first end (51a) of the pre-infusion line (51).P51117PC00

[0146] In a 105thaspect according to any one of the preceding aspects in combination with aspect 101, the first end (51a) of the pre-infusion line (51) is interposed between the second end (6b) of the blood withdrawal line (6) and the blood pump tract (6p) of the blood withdrawal line (6).

[0147] In a 106thaspect according to any one of the preceding aspects in combination with aspect 101, the pre-infusion line (51) comprises a respective pre-infusion pump tract (51 p) interposed between the first end (51a) and the second end (51b) of the pre-infusion line (51), the infusion pump tract (51 p) of the pre-infusion line (51) being configured to be engaged by an pre-infusion peristaltic pump (54) configured to deliver a substance contained in the pre-infusion substance source (10) from said pre-infusion substance source (10) to the blood withdrawal line (6).

[0148] In a 107thaspect according to any one of the preceding aspects in combination with aspect 100, the disposable set comprises a syringe pump (9) fluidly connected to the blood withdrawal line (6) at a syringe access, said syringe access being interposed between the blood pump tract (6p) and the treatment unit (101), said syringe pump (9) being configured to contain an anticoagulation substance, optionally said anticoagulation substance including heparin.

[0149] In a 108thaspect according to any one of the preceding aspects in combination with aspect 100, the blood withdrawal line (6) comprises a syringe access configured to fluidly connect to a syringe pump (9), said syringe access being interposed between the blood pump tract (6p) and the treatment unit (101), said syringe pump (9) being configured to contain an anticoagulation substance, optionally said anticoagulation substance including heparin.

[0150] In a 109thaspect according to any one of the preceding aspects, said treatment unit (101) comprises a filtration unit (2) having a primary chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5), wherein the blood circuit (17) includes said primary chamber (3) of the filtration unit (2).

[0151] In a 110thaspect according to the preceding aspect, the disposable set further includes a fluid circuit comprising:

[0152] - an effluent fluid line (13) extending between a first end connected to an outlet of the secondary chamber (4) of the treatment unit (101), and a second end for connection to a drain or a collection container (62), - a dialysis liquid supply line (8) extending between a first end connected to an inlet of the secondary chamber (4) of the treatment unit (101), and a second end for connection to a dialysis fluid source (14), optionally said dialysis fluid source (14) including a bag or a dialysis preparation unit of the extracorporeal blood treatment apparatus (1).

[0153] In a 111thaspect according to any one of the preceding aspects, the fluid circuit comprises an infusion branch (58) fluidly connecting the dialysis liquid supply line (8) to the blood circuit (17), in particular to the auxiliary fluid infusion inlet (91) of the degassing chamber (80) or to the auxiliary fluid infusion line (63).

[0154] In a 112thaspect according to any one of the preceding aspects, the degassing chamber (80) includes a fluid deviator (94) positioned in the inner volume (86) of the degassing chamber (80).

[0155] In a 113thaspect according to the preceding aspect, the fluid deviator (94) delimits, within the inner volume (86), an annular chamber configured to allow fluid and / or blood to flow towards the blood outlet (82) of the degassing chamber (80).P51117PC00

[0156] In a 114thaspect according to any one of the preceding aspects in combination with aspect 112, the fluid deviator (94) has a cross section, defined along a plane orthogonal to the height direction (H), having circular shape. In a 115thaspect according to the preceding aspect, a diameter of said cross section of the fluid deviator (94) varies along the height direction (H).

[0157] In a 116thaspect according to the preceding aspect, a diameter of said cross section of the fluid deviator (94) varies along the height direction (H) according to a curved profile, optionally according to a semicircular profile. In a 117thaspect according to any one of the preceding aspects in combination with aspect 112, the fluid deviator (94) comprises an external surface (94a) having concave shape.

[0158] In a 118thaspect according to the preceding aspect, said external surface (94a) faces the blood inlet (81) of the degassing chamber (80).

[0159] In a 119thaspect according to the preceding aspect, said external surface (94a) faces the auxiliary fluid infusion inlet (91) of the degassing chamber (80).

[0160] In an aspect 119 bis according to any one of the preceding aspects in combination with aspect 112, the fluid deviator (94) is positioned upstream to the reduced passage (88) of the degassing chamber.

[0161] In an aspect 119 ter according to any one of the preceding aspects in combination with aspect 112, the fluid deviator (94) is positioned in the main housing (87) of the degassing chamber.

[0162] In an aspect 119 quater according to any one of the preceding aspects in combination with aspect 112 and 26, the fluid deviator (94) comprises an extremal portion having conical shape, said extremal portion facing the conical bottom portion 87a of the main housing 87 of the degassing chamber.

[0163] Pressure valve 76 as dependent aspect (Pulsed infusion with pressure valve 76 on the infusion line) In an aspect 119 quinquies according to any one of the preceding aspects, the disposable set (100) comprises a pressure valve (76) located on the fluid infusion line (74) and interposed between the first end (74a) and the second end (74b) of the fluid infusion line (74), the pressure valve (76) being movable between a flow position and an interception position, wherein the pressure valve (76) is configured to switch:

[0164] from the interception position to the flow position when a differential pressure across the pressure valve (76) exceeds an aperture pressure (P1); and

[0165] from the flow position to the interception position when said differential pressure across the pressure valve (76) falls below a closure pressure (P2);

[0166] wherein the closure pressure (P2) is below the aperture pressure (P1 ).

[0167] In an aspect 119 sexies, the aspect 119 quinquies is according to any one of the following aspects from 121 to 173.

[0168] In an aspect 119 septies, the aspect 119 quinquies is according to aspect 179.

[0169] Independent aspect on Pressure valve 76 (Pulsed infusion with pressure valve 76 on the infusion line) An aspect 120 is directed to a disposable set (100) for an extracorporeal blood treatment apparatus (1), the disposable set (100) comprising:

[0170] an optional treatment unit (101);P51117PC00

[0171] a blood circuit (17) comprising:

[0172] o a blood withdrawal line (6) extending between a first end (6a) connected / to be connected to the treatment unit (101) and a second end (6b) for connection to a patient, o a blood return line (7) extending between a first end (7a) connected / to be connected to the treatment unit (101) and a second end (7b) for connection to the patient;

[0173] a fluid infusion line (74) extending between a first end (74a) connected to the blood circuit (17) and a second end (74b) for connection to an infusion substance source (11) configured to contain an infusion fluid, a pressure valve (76) located on the fluid infusion line (74) and interposed between the first end (74a) and the second end (74b) of the fluid infusion line (74), the pressure valve (76) being movable between a flow position and an interception position, wherein the pressure valve (76) is configured to switch:

[0174] o from the interception position to the flow position when a differential pressure across the pressure valve (76) exceeds an aperture pressure (P1); and

[0175] o from the flow position to the interception position when said differential pressure across the pressure valve (76) falls below a closure pressure (P2);

[0176] wherein the closure pressure (P2) is below the aperture pressure (P1 ).

[0177] In a 121staspect according to the preceding aspect, the pressure valve (76), after switching from the interception position to the flow position, is configured to maintain the flow position as long as said differential pressure is greater than the closure pressure (P2).

[0178] In a 122ndaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76), when in the interception position, is configured to maintain the interception position up to the aperture pressure (P1).

[0179] In a 123rdaspect according to any one of the preceding aspects in combination with aspect 120, the differential pressure is defined between a valve inlet of the pressure valve (76) and a valve outlet of the pressure valve (76).

[0180] In a 124thaspect according to the preceding aspect, the valve inlet faces an upstream tract of the fluid infusion line (74) towards the second end (74b) of the fluid infusion line (74), and the valve outlet faces a downstream tract of the fluid infusion line (74) towards the first end (74a) of the fluid infusion line (74).

[0181] In a 125thaspect according to any one of the preceding aspects in combination with aspect 123, the pressure valve (76) is configured to switch from the interception position to the flow position when a fluid pressure at the valve inlet is higher than a fluid pressure at the valve outlet by at least said differential pressure.

[0182] In a 126thaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76), when arranged in the flow position, is configured to allow a fluid flow in the fluid infusion line (74) from the second end (74b) to the first end (74a) of the fluid infusion line (74).

[0183] In a 127thaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76), when arranged in the interception position, is configured to prevent, or reduce with respect to the flow position, a fluid flow in the fluid infusion line (74) from the second end (74b) to the first end (74a) of the fluid infusion line (74).P51117PC00

[0184] In a 128thaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76) is a passive valve configured to switch between the flow position and the interception position based on said differential pressure, in particular wherein said pressure valve (76) is not controlled by a control unit or an electronic circuit.

[0185] In a 129thaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76) is a bi-stable valve comprising a first stable position defined by the flow position, and a second stable position defined by the interception position.

[0186] In a 130thaspect according to any one of the preceding aspects in combination with aspect 120, a fluid passage cross section of the pressure valve (76), when the pressure valve (76) switches from the interception position to the flow position, is configured to move from:

[0187] a minimal or zero fluid passage cross section (Smin) of the interception position, to

[0188] a maximum fluid passage cross section (Smax) of the flow position.

[0189] In a 131staspect according to the preceding aspect, the fluid passage cross section of the pressure valve (76) is maximum as soon as the pressure valve (76) switches from the interception position to the flow position. In a 132ndaspect according to any one of the preceding aspects in combination with aspect 130, the minimal or zero fluid passage cross section corresponds to a maximum closing passage section of the pressure valve (76), optionally wherein the zero fluid passage cross section (Smin) defines a closed fluid passage.

[0190] In a 133rdaspect according to any one of the preceding aspects in combination with aspect 130, the maximum fluid passage cross section (Smax) corresponds to a maximum size of the fluid passage cross section of the pressure valve (76).

[0191] In a 134thaspect according to any one of the preceding aspects in combination with aspect 130, the fluid passage cross section of the pressure valve (76) is configured to reduce from said maximum fluid passage cross section to said minimal or zero fluid passage cross section as the differential pressure drops from the aperture pressure (P1) to and below the closure pressure (P2).

[0192] In a 135thaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76) is a duckbill valve or a cross-cut valve or a cross-slit valve.

[0193] In a 136thaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76) is in one piece.

[0194] In a 137thaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76) is made of a silicone or rubber or plastic material.

[0195] In a 138thaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve is deformable between the flow position and the interception position.

[0196] In a 139thaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76) comprises a diaphragm (78) having a dome or hemispherical shape at least when arranged in the interception position.

[0197] In a 140thaspect according to the preceding aspect, the diaphragm (78 ) is deformable to switch between the flow position and the interception position.P51117PC00

[0198] In a 141staspect according to any one of the preceding aspects in combination with aspect 139, said diaphragm includes at least one through cut (77) configured to selectively allow and prevent fluid flow.

[0199] In a 142ndaspect according to the preceding aspect, when the pressure valve (76) is in the interception position, the through cut is closed to prevent or reduce fluid flow in the fluid infusion line (74).

[0200] In a 143rdaspect according to any one of the preceding aspects in combination with aspect 141, when the pressure valve (76) is in the flow position, the through cut is open to allow fluid flow in the fluid infusion line (74). In a 144 aspect according to any one of the preceding aspects in combination with aspect 139, the domeshaped or hemispherical diaphragm deforms, optionally inverts, its concavity when switching between the flow position and the interception position.

[0201] In a 145thaspect according to any one of the preceding aspects in combination with aspect 139, the domeshaped or hemispherical diaphragm defines a convex side (76a) and a concave side (76b).

[0202] In a 146thaspect according to the preceding aspect, when the pressure valve (76) is in the interception position, the convex side (76a) faces the upstream tract of the fluid infusion line (74) and the concave side (76b) faces the downstream side of the fluid infusion line (74).

[0203] In a 147thaspect according to any one of the preceding aspects in combination with aspect 141, the at least one through cut (77) comprises a first through cut and a second through cut crossing each other optionally orthogonally.

[0204] In a 148thaspect according to the preceding aspect, the first through cut intersects the second through cut at a midpoint of the second through cut.

[0205] In a 149thaspect according to any one of the two preceding aspects, the second through cut intersect the first through cut at a midpoint of the first through cut.

[0206] In a 150thaspect according to any one of the preceding aspects in combination with aspect 120, the aperture pressure (P1) is comprised between 0.5 bar and 10 bar.

[0207] In a 151staspect according to any one of the preceding aspects in combination with aspect 120, the closure pressure (P2) is comprised between 0 bar and 0.5 bar.

[0208] In a 152ndaspect according to any one of the preceding aspects in combination with aspect 120, the aperture pressure (P1) is at least 50% greater than the closure pressure (P2).

[0209] In a 153rdaspect according to any one of the preceding aspects in combination with aspect 120, a pressure difference between the aperture pressure (P1) and the closure pressure (P2) is comprised between 0.2 bar and 5 bar.

[0210] In a 154thaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76), when in the interception position, is configured to stop fluid flow in the fluid infusion line (74) from the second end (74b) towards the first end (74a).

[0211] In a 155thaspect according to any one of the preceding aspects in combination with aspect 120, the fluid infusion line (74) comprises at least a tract made of a silicone material, optionally wherein the fluid infusion line (74) is entirely made of silicone material.P51117PC00

[0212] In a 156thaspect according to any one of the preceding aspects in combination with aspect 120, the fluid infusion line (74) comprises at least a tract made of a medical grade plastic material, optionally wherein the fluid infusion line (74) is entirely made of a medical grade plastic material.

[0213] In a 157thaspect according to the preceding aspect, the medical grade plastic material includes polyvinyl chloride (“PVC”).

[0214] In a 158thaspect according to any one of the preceding aspects, a tract of the fluid infusion line (74) between said pressure valve (76) and the pump tract (74p) of the fluid infusion line (74) defines a compliant circuit section, the compliant circuit section comprising either or both:

[0215] • a compliant tube made of a flexible elastic material such as silicone or PVC; and / or

[0216] • a compliant chamber (96) located along the tract.

[0217] Notably, the compliant chamber (96) may be a bubble trap that is located downstream of the infusion pump (75) and upstream of the pressure valve (76).

[0218] In a 159thaspect according to any one of the preceding aspects in combination with aspect 120, the fluid infusion line comprises a pump tract (74p) configured to be coupled to an infusion pump (75) of the extracorporeal blood treatment apparatus (1), said pump tract (74p) being interposed along the fluid infusion line (74) between the pressure valve (76) and the second end (74b) of the fluid infusion line (74).

[0219] In a 160thaspect according to the preceding aspect, the pump tract (74p) of the fluid infusion line (74) is upstream with respect to the pressure valve (76).

[0220] In a 161staspect according to any one of the preceding aspects in combination with aspect 120, the tract of the fluid infusion line (74) between said pressure valve (76) and the pump tract (74p) of the fluid infusion line (74) defines an inner volume configured to house fluid, wherein said inner volume is comprised between 0.1 ml and 15 ml, in particular wherein said inner volume is measured in a rest condition wherein no pressure is applied inside the infusion line (74).

[0221] In a 162ndaspect according to any one of the preceding aspects in combination with aspect 130, at a rest condition, the infusion line (74) comprises an inner lumen having a respective fluid passage cross section, wherein a ratio between the fluid passage cross section of the fluid infusion line (74) and the maximum fluid passage cross section (Smax) of the pressure valve (76) is comprised between 0,7 and 1 ,3, optionally between 0,85 and 1.2, optionally between 1 and 1,2.

[0222] In a 163rdaspect according to any one of the preceding aspects in combination with aspect 120, the first end (74a) of the fluid infusion line (74) is connected to the return line (7) in particular downstream the degassing chamber (80).

[0223] In a 164thaspect according to the preceding aspect, the blood return line (7) includes a 3-way connector, optionally a “T” connector, comprising a blood inlet connected to an upstream tract of the blood return line (7), a blood outlet connected to a downstream tract of the blood return line (7), and an infusion inlet connected to the first end (7a) of the fluid infusion line (74).P51117PC00

[0224] In a 165thaspect according to any one of the preceding aspects from 120 to 162, the disposable set (100) comprises a degassing chamber (80) arranged on the blood return line (7) between the first end (7a) and the second end (7b) of the blood return line (7), said degassing chamber (80) comprising:

[0225] a blood inlet (81) for blood entry;

[0226] a blood outlet (82) for blood output;

[0227] a fluid infusion inlet (83) connected to the first end (74a) of the fluid infusion line (74).

[0228] In a 166thaspect according to the preceding aspect, said fluid infusion inlet (83) of the degassing chamber (80) is interposed between said blood inlet (81) and said blood outlet (82) of the degassing chamber (80).

[0229] In a 167thaspect according to any one of the two preceding aspects, the degassing chamber (80) is according to any one of the aspects from 1 to 119.

[0230] In a 168thaspect according to any one of the preceding aspects in combination with aspect 120, at a rest condition, wherein no differential pressure is applied across the pressure valve (76) or wherein said differential pressure is below the closure pressure (P2), the pressure valve (76) keeps the interception position in a stable manner passively.

[0231] In a 169thaspect according to any one of the preceding aspects in combination with aspect 120, the disposable set comprises an infusion substance source (11) fluidly connected to the second end (74b) of the fluid infusion line (74), said infusion substance source (11) being a calcium solution source or a calcium solution bag containing or configured to contain a calcium solution fluid.

[0232] In a 170thaspect according to aspect 158, the compliant tube has an inner volume increasing between 0.5 ml and 4 ml every 1 bar pressure increase.

[0233] In a 171staspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve is configured to perform a pulsed infusion of the infusion fluid in the blood circuit.

[0234] In a 172ndaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve is at a maximum distance from the first end (7a) of the fluid infusion line (74) less than 100 mm, optionally less than 50 mm, optionally comprised between 5 mm and 100 mm.

[0235] In a 173rdaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76) is configured to allow fluid flow in a direction from the second end (74b) of the infusion line (74) towards the first end (74a) of the infusion line (74), and from the first end (74a) of the infusion line (74) towards the second end (74b) of the infusion line (74).

[0236] In an aspect 174, the aspect 119 quinquies is according to any one of aspects from 121 to 173.

[0237] In a 175thaspect according to any one of the preceding aspects in combination with aspect 120, the pressure valve (76) is configured, by switching from the interception position to the flow position and vice versa, to generate a pulsed infusion of the infusion fluid into the blood circuit (17), wherein each pulse has a duration (T) and two subsequent pulses are separated by a bolus period (Tboius), a dimensionless factor (a) being defined as:

[0238] T

[0239] a = - T1bolusP51117PC00

[0240] wherein:

[0241] a is the dimensionless factor comprised between 0 and 1;

[0242] T is the pulse duration; and

[0243] Tboius is a time between two subsequent pulses (e.g., expressed in minutes).

[0244] In a 176thaspect according to the previous aspect, the dimensionless factor (a) is lower than 0.7, in particular lower than 0.6 and more in detail lower than 0.5.

[0245] High values of parameter a are at risk of clotting as similar to the continuous infusion process. An upper value of 0.7 is considered to be the maximum value to reduce clotting effect. 0.6 is a more appropriate value, while 0.5 will be considered reasonable for the parameter a.

[0246] In a 177thaspect according to any one of the preceding aspects 175 and 176, the dimensionless factor (a) is:

[0247] 20 15

[0248] a < 1 — — - and in particular a < 1 — — - ' bolus ' bolus

[0249] wherein:

[0250] Tboius is a time expressed in minutes.

[0251] Clearly, excessively long infusion periods without calcium infusion are not acceptable as creating a risk of periodic hypocalcaemia for the patient. An upper limit of 20 minutes looks reasonable in this respect for the (Tboius-T) time; 15 minutes is even a better maximum time interval.

[0252] In a 178thaspect according to any one of the preceding aspects 175 to 177, the dimensionless factor (a) is:

[0253] 1

[0254] oc> - 60 ' bolus

[0255] wherein:

[0256] Tboius is a time expressed in minutes.

[0257] Very short infusion times (T below 1 second) appear impractical and difficult to perform. This condition matches with the above relation.

[0258] Extracorporeal blood treatment apparatus

[0259] A 179thaspect is directed to an extracorporeal blood treatment apparatus (1) comprising the disposable set (100) according to any one of the preceding aspects in combination with aspect 120, wherein the extracorporeal blood treatment apparatus (1) comprises:

[0260] a blood pump (21) configured to engage a respective blood pump tract (6p) of the blood withdrawal line (6);

[0261] an infusion pump (75) configured to engage a respective pump tract (74p) of the fluid infusion line (74); a control unit (12) operatively connected to the blood pump (21) and the infusion pump (75), said control unit being configured to perform a pulsed infusion procedure comprising a step to run the infusion pump (75) at a set speed to deliver fluid through said pressure valve (76).

[0262] In a 180thaspect according to the preceding aspect, said pressure valve (76), during an operating condition wherein the infusion pump (75) runs at said set speed, is configured to deliver fluid towards the first end (74a) of the fluid infusion line (74) intermittently over time.P51117PC00

[0263] In a 181staspect according to any one of the preceding aspects 179 and 180, said set speed of the infusion pump (75) is a constant speed defining a substantially constant flow rate (Qca) in the fluid infusion line (74) at an immediate pump outlet. Clearly, the flow dynamic / time dependence evolves along the fluid infusion line (74) depending on how compliance is provided (homogeneous along the tube or ocal' if a chamber is placed along the line). Said in other words, the control unit (12) drives the infusion pump (75) according to a set infusion flow rate Qca(that is constant over a treatment interval)

[0264] In a 182ndaspect according to the preceding aspect 181, during the pulsed infusion, a dimensionless factor (a) is defined as:

[0265] Qca

[0266] a = — —

[0267] Qinf

[0268] wherein:

[0269] a is the dimensionless factor comprised between 0 and 1;

[0270] Qca is the substantially constant flow rate in the fluid infusion line (74) at the pump outlet (or the set infusion flow rate for the infusion pump); and

[0271] Qinf is the mean flow during an opening phase of the valve.

[0272] In a 183rdaspect according to any one of the preceding aspects 180 to 182, said set speed of the infusion pump (75) is configured to define a flow rate in the infusion line (74) up to 200 ml / h (max) and comprised between 2 ml / h and 200 ml / h; specifically 3 ml / h to 50 ml / h.

[0273] Of course, the infusion flow rate depends on the calcium concentration (e.g., 50-500 mmol / L, optionally 200-400 mmol / L), the blood flow rate (e.g., 100-200 ml / min) and the amount of calcium removed by the dialyzer. Therefore, the mentioned flow rate values are just indicative.

[0274] In a 184thaspect according to any one of the preceding aspects 180 to 183, the extracorporeal blood treatment apparatus (1) comprises an air bubble sensor (55) located on the blood return line (7), the infusion line (74) is designed to infuse the infusion fluid upstream of the air bubble sensor (55).

[0275] Method for infusing an infusion fluid in the blood circuit

[0276] A 185thaspect is directed to a method for infusing an infusion fluid in a blood circuit (17) of a disposable set (100) for an extracorporeal blood treatment apparatus (1), said method comprising at least the following steps:

[0277] providing a disposable set (100) according to any one of the preceding aspects, wherein the infusion substance source (11) is a calcium solution source or a calcium solution bag containing a calcium solution fluid;

[0278] infusing the calcium solution fluid in the blood circuit (17) by running an infusion pump (75) of the extracorporeal blood treatment apparatus (1), the infusion pump (75) engaging a pump tract (74p) of the fluid infusion line (74).

[0279] In a 186thaspect according to the preceding aspect, the disposable set (100) is according to any one of aspects 1 , 2, or 120 and any of their depending aspects.P51117PC00

[0280] DRAWINGS

[0281] Some embodiments and some aspects of the invention will be described below with reference to the attached drawings, provided for illustrative purposes only, wherein:

[0282] Figure 1 is a schematic view of an extracorporeal blood treatment apparatus with a disposable set according to the present invention;

[0283] Figure 2 is a schematic view of an extracorporeal blood treatment apparatus with a further embodiment of a disposable set according to the present invention;

[0284] Figure 3 is perspective view of a degassing chamber of the disposable set according to the present invention;

[0285] Figure 4 is a perspective bottom view of the degassing chamber according to the present invention; Figure 5 is a lateral plane view of the degassing chamber according to the present invention;

[0286] Figure 6 is a cross-sectional view of the degassing chamber along the plane shown in figure 5;

[0287] Figure 7 shows the fluid deviator of the degassing chamber;

[0288] Figure 8 is a cross-sectional view of the degassing chamber, along the plane shown in figure 5, including the fluid deviator;

[0289] Figure 9 shows an embodiment of the pressure valve of the fluid infusion line;

[0290] Figure 10 is a cross sectional view of the pressure valve of figure 9;

[0291] Figure 11 is a top view of the pressure valve of figure 9;

[0292] Figure 12 shows the pressure valve of figure 9 arranged on the fluid infusion line of figures 1, 2 and 16; Figure 13 shows a graph representing the trend of the flow rate Q of the infusion fluid in the infusion line over time t in an embodiment wherein the disposable set comprises the pressure valve;

[0293] Figure 14 shows a graph representing the pressure trend P experienced by the infusion fluid in the infusion line over time t in an embodiment wherein the disposable set comprises the pressure valve;

[0294] Figure 15 shows a graph representing the trend of the fluid passage cross section S of the pressure valve as a function of the differential pressure across the pressure valve in an embodiment wherein the disposable set comprises the pressure valve;

[0295] Figure 16 is a schematic view of an extracorporeal blood treatment apparatus with a disposable set comprising the pressure valve according to the present invention, wherein the fluid infusion line is directly connected to the return line of the blood circuit;

[0296] Figure 17 is an illustration of the operating range of potential interest for periodic calcium bolus infusion.

[0297] DEFINITIONS

[0298] In this detailed description, corresponding parts illustrated in the various figures are indicated with the same numerical references. The figures may illustrate the invention through non-scaled representations; therefore, parts and components illustrated in the figures relating to the object of the invention may relate exclusively to schematic representations.P51117PC00

[0299] The terms “upstream" and “downstream" refer to a direction or trajectory of advancement of a fluid configured to flow within the fluid line during normal usage of the apparatus, for example during an extracorporeal blood treatment or during a priming procedure of the disposable set. During normal use of the apparatus the blood pump pumps blood from the patient vascular access along the blood withdrawal line towards an inlet of the filtration unit, and back to the patient from an outlet of the filtration unit along the blood return line towards the patient. Infusion fluids are infused from the respective fluid sources towards the blood circuit and into the blood. Dialysis fluid (if any) flows from the dialysis line to the filtration unit and towards the effluent line. Blood flow and dialysis flow are countercurrent in the filtration unit.

[0300] We define the “dialysis fluid’ as the treatment fluid introduced to the second chamber of the filtration unit 2. The dialysis fluid may be on-line prepared or pre-packaged in sterile bags. Usually in CRRT apparatuses / applications the dialysis fluid, but also the replacement fluids (possibly also regional anticoagulant fluid and / or ion re-establishing solution fluid) are contained in (disposable) containers or bags.

[0301] We define the “dialysate" or “effluent’ as the fluid flowing out from the outlet of the second chamber of the filtration unit 2. Dialysate or effluent is the spent dialysis fluid, comprising the uremic toxins removed from the blood and may include ultrafiltrate fluid.

[0302] We define “regional anticoagulant’ an anticoagulant substance that is used locally in the dialysis circuit to prevent blood clotting and which, once mixed with extracorporeal blood, is quickly metabolized by the patient, thus avoiding systemic anticoagulation.

[0303] We define a “ion reestablishing solution" a solution used during the extracorporeal blood treatment to restore the balance of essential ions (such as calcium, magnesium, and potassium) in the blood. In the case of citrate being used as an anticoagulant in regional anticoagulation during dialysis, an ion reestablishing solution is a solution that typically contains calcium (and other electrolytes), usually in a concentration higher than the physiological concentration in the blood.

[0304] We define the term “degassing as a process wherein gases dissolved in a fluid, such as an infusion fluid or blood, tend to get free due to the fluid flow, a local low pressure and / or due to fluid warming, which leads to separation of the gases from the liquid phase of the fluid, consequently generating gas bubbles into the fluid. A degassing chamber promotes both degassing and collection of gas bubbles (already present in the fluid or formed due to the degassing effect) in an upper portion of the chamber occupied by an air volume.

[0305] We define “negative pressure" a pressure below the local atmospheric pressure.

[0306] We define “positive pressure" a pressure above the local atmospheric pressure.

[0307] DETAILED DESCRIPTION

[0308] Disposable blood treatment set 100

[0309] Reference number 100 is directed to a disposable set for an extracorporeal blood treatment apparatus 1, such as a hemodialysis apparatus for performing a haemodialysis treatment (HD), an ultrafiltration apparatus forP51117PC00

[0310] performing an ultrafiltration treatment (UP), a haemofiltration apparatus for performing a haemofiltration treatment (HF) or a haemodiafiltration apparatus for performing a haemodiafiltration treatment (HDF).

[0311] Alternatively, the disposable set 100 may be used to perform an extracorporeal blood treatment such as a Therapeutic Plasma Exchange (TPE) treatment. The TPE treatment is a procedure wherein the patient's blood passes through an apheresis machine for plasma filtration and removal: plasma is then replaced by a replacement fluid, such as a plasma from a donor, albumin, or saline.

[0312] Alternatively, the disposable set 100 may be used to perform an extracorporeal blood treatment such as a HemoPerfusion treatment for blood purification: in particular, the HemoPerfusion treatment consists of the passage of the patient's blood through a device, usually a column, which contains adsorbent particles configured to remove toxins from blood, i.e. in case of treatment of poisoning.

[0313] Alternatively, the disposable set 100 may be used to perform an extracorporeal blood treatment for removing CO2 from the blood: the CO2 removal treatment may be performed during a dialysis treatment or may be performed by itself through a blood circuit ad hoc.

[0314] Furthermore, the disposable set 100 may be connected to an extracorporeal blood treatment apparatus for blood oxygenation, namely an Extracorporeal Membrane Oxygenation ECMO treatment apparatus.

[0315] According to one or more of the medical fields listed above, an exemplificative disposable set 100, schematically shown in figures 1, 2 and 16, is directed in a non-limitative way to haemodialysis treatment and comprises blood lines and fluid lines configured to be associated to the respective treatment apparatus 1, the latter including peristaltic pumps to promote fluid flow and respective sensors and actuators to operate the circuit. Here after a detailed, but not limitative, description of the disposable set 100 is provided. In this regard, the pumps are not part of the disposable set 100, although shown in figures 1, 2 and 16 for sake of simplicity. Notably, also the syringe pump 9 and bags 10, 11, 14, 62, 64 may be part or not of the disposable set 100 depending on its configuration.

[0316] The disposable set 100 comprises at least one treatment unit 101 which is configured to treat the blood withdrawn from the patient. The treatment unit 101 may include a gas exchanger and / or a filtration unit 2. The filtration unit 2 may comprise a filter configured for performing one between a haemodialysis treatment (HD), an ultrafiltration treatment (UF), a haemofiltration treatment (HF) and a haemodiafiltration treatment (HDF). The filtration unit 2 may alternatively be an absorber unit, or sorbent cartridge for a sorbent system in case of hemoperfusion treatments. The gas exchanger may be used for blood oxygenation and / or for CO2 removal from blood.

[0317] In an embodiment, the filtration unit 2 has a primary chamber 3 and a secondary chamber 4 separated by a semi-permeable membrane 5, wherein the primary chamber 3 receives the blood withdrawn from the patient, while the secondary chamber 4 receives waste products and fluid removed from the blood and discharges it through an outlet connected to an effluent fluid line 13. Depending upon the treatment, the membrane 5 of the filtration unit 2 may be selected to have different properties and performances. According to a further embodiment, the secondary chamber 4 of the filtration unit 2 further comprises, in addition to the outlet, an inletP51117PC00

[0318] configured to receive fluid, i.e. dialysis fluid, from a dialysis liquid supply line 8. The dialysis liquid supply line 8 and the effluent fluid line 13 are part of a dialysis fluid circuit.

[0319] The blood circuit 17 of the disposable set 100 comprises a blood withdrawal line 6 extending between a second end 6b for connection to the vascular circuit of the patient P and a first end 6a connected to the filtration unit 2. In case the filtration unit 2 comprises the primary and secondary chambers, the blood withdrawal line 6 is connected to the inlet of the primary chamber 3 of the filtration unit 2. The blood withdrawal line 6 is configured to receive blood from the patient P and carry the blood along a withdrawal direction 200 from the second end 6b to the first end 6a of the blood withdrawal line 6.

[0320] The blood circuit 17 further comprises a blood return line 7 extending between a first end 7a connected to the filtration unit 2 and a second end 7b for connection to said patient P. In case the filtration unit 2 comprises the primary and secondary chambers, the blood return line 7 is connected to the outlet of the primary chamber 3 of the filtration unit 2. The blood return line 7 is configured to receive blood from the outlet of the filtration unit 2 and carry the blood along a return direction 200 defined from the first end to the second end of the blood return line 7.

[0321] The withdrawal line 6 and the return line 7 may be connected to the blood stream of the patient through a vascular access, through a needle, a catheter, or an access device. The withdrawal line 6 and the return line 7 may be made of a flexible material, for example PVC or other plastic based bio compatible material: the blood lines 6, 7 may also be transparent to allow an operator to see the blood flowing within the lines.

[0322] The blood withdrawal line 6 includes a pump tract 6p configured to be engaged by a blood pump 21 of the extracorporeal blood treatment apparatus 1 configured to generate a blood flow so that blood circulates in the blood circuit in the direction 200 from the blood withdrawal line 6 towards the filtration unit 2. In one example, the blood-pump 21 may be implemented by a peristaltic pump. The blood pump tract 6p may be a portion of the blood withdrawal line 6 itself, which is interposed and extends between the first end 6a and the second end 6b of the blood withdrawal line 6.

[0323] Thus, the blood withdrawal line 6 comprises the blood pump tract 6p, a first tract extending between the first end 6a and the blood pump tract 6p, and a second tract extending between the second end 6b of the blood withdrawal line 6 and the blood pump tract 6p.

[0324] The blood pump tract 6p may be different with respect to the first and the second tracts of the blood withdrawal line 6 in terms of dimension and / or material. In particular the blood pump tract 6p may have an external dimension, i.e. an external diameter, bigger than an external dimension, i.e. an external diameter, of the first and / or second tracts of the blood withdrawal line. The blood pump tract 6p may also has a stiffness / elasticity different from a stiffness of the first and the second tracts of the blood withdrawal line 6: for example, the blood pump tract 6p may be made by a more flexible / elastic material with respect to a material of the first and / or second tracts, in order to withstand the fatigue stresses caused by the peristaltic pump 21 of the external blood treatment apparatus.

[0325] The blood circuit 17 further comprises a pre-infusion line 51 extending between a first end 51 a connected to the blood withdrawal line 6 upstream the blood pump tract 6p at a fluid access 50, and a second end 51b forP51117PC00

[0326] connection to a pre-infusion substance source 10. The blood pump tract 6p is interposed between the filtration unit 2 and the first end 51 a of the pre-infusion line 51.

[0327] The pre-infusion substance source 10 connected to the infusion line 51 may be an infusion bag. The bag may house a fluid infusion solution comprising a replacement solution or a regional anticoagulant solution, such as citrate (e.g., trisodium citrate or citric acid or a mix thereof). The latter being usually the most common embodiment. Notably, the disposable set 100 may comprise the bag, which is connected to the second end 51b of the pre-infusion line 51.

[0328] The infusion line 51 may further comprise a respective pre-infusion pump tract 51 p interposed between the first end 51 a and the second end 51 b of the pre-infusion line 51 : the pre-infusion pump tract 51 p of the pre-infusion line 51 is configured to be engaged by a pre-infusion pump 54, i.e. a peristaltic pump, configured to determine, during an operating condition of the pre-infusion pump 54, a pressure downstream the pre-infusion pump tract 51 p higher that the pressure at the junction point 50 to allow infusion fluid to flow in a direction from the second to the first end of the pre-infusion line 51 towards the blood withdrawal line 6.

[0329] The blood circuit 17 comprises an injection point where the pre-infusion line 51 connects to the blood withdrawal line 6 to allow the infusion fluid, flowing within the pre-infusion line 51, to be infused into the blood withdrawal line 6: in particular, the injection point may include an infusion connector.

[0330] Following the direction of blood circulation 200, in case the apparatus is also configured to remove CO2 a gas exchanger 96 for removing CO2 from circulating blood may be connected to the blood circuit 17. The gas exchanger 96 is in fluid communication with the blood circuit 17 to receive extracorporeal blood, allow CO2 removal from blood and returning blood to the blood circuit at a downstream point.

[0331] As mentioned, blood circulation direction during normal use of the apparatus is indicated in figure 1 with an arrow 200 which also represents the blood flow rate Qb direction during treatment. The gas exchanger is connected in series with the filtration unit 2 and is placed on the return line 7. The gas exchanger has a blood chamber and a gas chamber separated by a membrane permeable to gases, in particular CO2; the gas exchanger 96 comprise a gas inlet, which may be connected to a gas source, such as the medical gas supply system in a hospital to receive pressurized air or oxygen for example, and a gas outlet in fluid communication with the gas chamber to discharge exhausted gas having removed CC from extracorporeal blood. The blood inlet and the blood outlet put the extracorporeal blood circuit 17 in fluid communication with the gas exchanger blood chamber. The gas exchanger may be alternatively positioned upstream of the filtration unit on the blood withdrawal line 6. Of course, the gas exchanger is not part of the dialysis machine if CO2 removal is not required for treatment. As a further possibility, the gas exchanger may be the exclusive treatment unit 101, i.e., no filtration unit 2 is present in the circuit.

[0332] The dialysis fluid circuit comprises the effluent fluid line 13 connected to the outlet of the filtration unit 2: the effluent fluid line 13 may also comprise a respective effluent pump tract 13p configured to be engaged to a effluent pump 26. The fluid to be eliminated then passes through a blood detector 61 and is conveyed into a collection container or bag 62. The effluent fluid line 13 may also comprise a pressure access 60 connectable to a pressure sensor of the apparatus to monitor the fluid pressure in the effluent fluid line 13.P51117PC00

[0333] Analogously, in the case wherein the dialyzer comprises an inlet, the disposable set may comprise a dialysis liquid supply line 8 connected to the inlet of the filtration unit 2 and configured to deliver dialysis fluid into the secondary chamber 4 of the filtration unit 2. The dialysis liquid supply line 8 may also comprise a respective supply pump tract 8p configured to be engaged to a dialysis fluid pump 25 of the extracorporeal blood treatment apparatus. The supply line 8 extends between a first end connected to the inlet of the secondary chamber of the filtration unit 2, and a second end connected or connectable to a container 14. The container 14 may comprise a fluid bag containing or configured for containing dialysis fluid or a replacement fluid.

[0334] Downstream from the dialysis fluid pump 25 in the direction of circulation 300 there is a branching 56 splitting the dialysis supply line 8 up into an intake branch 57 and an infusion branch 58. In particular, the infusion branch 58 is connected to the blood return line 7 of the blood circuit 17. In other words, through said infusion branch 58 it is possible to obtain a post-infusion directly in the blood line 17 using the content of the primary fluid container. As shown in figure 1, the infusion branch 58 fluidly connects the dialysis liquid supply line 8 to an auxiliary fluid infusion inlet 91 of the degassing chamber 80 or to the auxiliary fluid infusion line 63, so that the fluid contained in the container 14 may be infused downstream the filtration unit 2, in particular in the degassing chamber 80.

[0335] Conversely, the intake branch 57 conveys the fluid directly to the filtration unit 2 and in particular to the secondary chamber of said unit. The dialysis fluid circuit is further equipped with a selector 59 for determining the percentages of fluid flow within the infusion branch 58 and the intake branch 57. Generally said selector 59, usually placed near the branching 56, may be positioned at least between a first operating condition in which it allows the passage of fluid in the intake branch 57 and blocks the passage in the infusion branch 58, and a second operating condition in which it allows the passage of fluid in the infusion branch 58 and blocks the passage in the intake branch 57. In other words, said selector 59 may consist of a valve element operating on the dialysis fluid circuit by alternatively blocking the passage of fluid in either branch. Suitable selectors may be alternatively provided, which are able to establish a priori the amount of liquid that has to pass through both branches simultaneously. It will also be possible to vary the percentages of fluid in either branch as a function of time and of the pre-established therapies. The dialysis liquid through the intake branch 57 gets into the secondary chamber 4 of the filtration unit 2. In particular, the primary chamber 3, through which the blood flow passes, is separated from the secondary chamber 4 through which the dialysis liquid passes through the semipermeable membrane 5 ensuring the suitable passage of the dangerous substances / molecules and of fluid from the blood towards the dialysis liquid mainly through convection and diffusion processes, and also ensuring through the same principles the passage of substances / molecules from the dialysis liquid towards the blood. The disposable set 100 also comprises a fluid infusion line 74 extending between a first end 74a connected to the blood circuit 17 and a second end 74b for connection to an infusion substance source 11. In particular, the first end 74a of the fluid infusion line 74 may be connected to a degassing chamber 80, as shown in figures 1 and 2, described later in detail. Alternatively, the first end 74a of the fluid infusion line 74 may be connected to the return line 7 downstream the degassing chamber 80, as shown in figure 16. The fluid infusion line 74 may be made by PVC, silicone, or other plastic based materials (in general medical grade materials). In detail, theP51117PC00

[0336] fluid infusion line 74 may be made by the same material as the blood withdrawal line 6 and the pre-infusion line 51. The fluid infusion line 74 further includes a respective pump tract 74p configured to be engaged by an infusion pump 75 of the extracorporeal blood treatment apparatus 1, which is configured to determine a fluid flow, at least during an operating condition, from the infusion substance source 11 to the blood circuit 17. The fluid infusion line 74 includes an inner lumen for the fluid flow having a lumen radius, and an external surface having an external radius: the difference between the external radius and the lumen radius defines a wall thickness the fluid infusion line 74. The fluid infusion line 74 may have a fluid passage section comprised between 0.7 mm2and 8 mm2or the fluid passage section may have a diameter comprised between 1 mm and 3 mm. More specifically, the inner diameter / lumen is comprised between 1.5 mm and 2 mm, being for example 1.8 mm.

[0337] The infusion substance source 11 may be a calcium solution source or a calcium solution bag containing or configured to contain a solution fluid with a high calcium concentration. The calcium solution fluid may be in liquid form, e.g. having a calcium concentration comprised between 50 mmol / L and 500 mmol / L (for example between 100 mmol / L and 450 mmol / L) of calcium chloride, calcium gluconate or mix thereof. Usually, bags with a concentration between 200 and 400 mmol / L are used.

[0338] The disposable set 100 may comprise an auxiliary fluid infusion line 63 extending between a first end 63a, connected to the degassing chamber 80, and a second end 63b for connection to an auxiliary infusion substance source 64. The auxiliary fluid infusion line 63 may be made by PVC, silicone, or other plastic based materials (medical grade). The auxiliary fluid infusion line 63 includes a respective pump tract 63p configured to be engaged by an auxiliary infusion pump 65 of the extracorporeal blood treatment apparatus 1 which is configured to determine a fluid flow, at least during an operating condition, from the auxiliary infusion substance source 64 to the degassing chamber 80.

[0339] The auxiliary infusion substance source 64 may comprise a fluid bag containing a replacement fluid. The substance contained in the auxiliary infusion substance source 64 may be a replacement fluid solution including electrolytes such as sodium, potassium, magnesium in a physiological value (i.e., a concentration value that the electrolyte assumes in the blood of a healthy subject). Notably, the substance contained in the auxiliary infusion substance source 64 may be either the same or different from the substance contained in the infusion substance source 11.

[0340] The infusion line 63 may comprise a pre-infusion branch 67 connected to the blood withdrawal line 6 of the blood circuit 17, so that the fluid contained in the infusion substance source 64 may be infused in the blood withdrawal line 6. In detail, the pre-infusion branch 67 may be connected to the blood withdrawal line 6 between the blood pump 6p and the filtration unit 2.

[0341] In further detail, downstream from the infusion pump 65 with respect to the direction of infusion, there is an infusion branching 68 splitting the infusion line 63 towards the blood withdrawal line 6 or towards the degassing chamber 80. A selector 70 may be provided for determining the percentage of liquid flow to be sent to the degassing chamber and to the pre-infusion branch 67. The selector 70 placed near the branching 68 may be switched between at least a first operating condition in which it allows the passage of fluid in the pre-infusionP51117PC00

[0342] branch 67 and blocks the passage towards the degassing chamber, and at least a second operating condition in which it allows the passage of fluid in the degassing chamber and blocks the passage in the pre-infusion branch 67. Obviously, the selector 70 may be configured to determine the percentage of fluid that has to pass in each of the two branches and to possibly vary it in time in accordance with the planned therapies. Notably, the flow rate through the pre-infusion branch / line 67 may be determined by proper control of the infusion pump 65 and selector 70. A control unit 12 of the extracorporeal blood treatment apparatus may be configured to control the selector 70 to define a desired amount of fluid flow in the blood withdrawal line 6 and in the blood return line 7.

[0343] As already mentioned, the disposable set 100 includes a degassing chamber 80, shown in detail in figures from 3 to 8, arranged on the blood return line 7 between the first end 7a and the second end 7b of the blood return line 7. The degassing chamber 80 is provided to trap and remove gas, e.g., air bubbles, from the blood flow in the return line 7 before infusing it into the patient. The degassing chamber 80, also known as bubble trap, includes an inner volume 86 for housing the blood.

[0344] The degassing chamber 80 comprises a blood inlet 81 for blood entry in an inner volume 86 of the degassing chamber 80: the blood inlet 81 is connected or connectable to a third end 7c of the return line 7. In an embodiment, the blood inlet 81 is irremovably coupled, e.g. heat or ultrasound welded or glued, to the third end 7c of the return line 7. Furthermore, the blood inlet 81 of the degassing chamber 80 defines a respective blood inlet access direction 81a representing the blood direction entering the inner volume 86 of the degassing chamber 80.

[0345] The blood inlet 81 includes an inner surface coupled in contact with the external surface of the blood return line 7: thus, the inner surface of the blood inlet 81 and the external surface of the blood return line 7 may have substantially the same diameter. The inner surface of the blood inlet 81 has circular shape according to a cross sectional view orthogonal to the blood inlet access direction 81a. Notably, given that the blood inlet 81 has cylindrical shape, the blood inlet access direction 81a corresponds to a longitudinal axis of said cylindrical shape. The inner surface of the blood inlet 81 may have a diameter comprised between 8.5 mm and 4 mm, for example 6.4 mm.

[0346] The blood inlet 81 may also comprise a stop portion 81c facing, and in particular contacting, a thickness wall of the third end 7c of the blood return line 7: the stop portion 81c may extend substantially orthogonal to the blood inlet access direction 81a. The thickness wall of the blood return line 7 defines a thickness of the blood return line 7 measured between an inner lumen and an external surface of the blood return line 7. The thickness of the blood return line 7 entering the degassing chamber 80 may be comprised between 0.75 mm and 1.5 mm and more particularly between 1 mm and 1.4 mm (e.g., is equal to 1.2 mm). Correspondingly, the stop portion 81c assumes corresponding ranges or value. The blood inlet 81 may include a rastered invitation (e.g., 2-4 mm long) to aid insertion of the blood tube during assembly. The rastered invitation reduces the entry hole from about 7.5 mm to about 6.6 / 6.4 mm. Downstream of the stop portion 81c the inlet passage section corresponds to the lumen passage section of the blood return line 7 and for example is about 4 mm.P51117PC00

[0347] The degassing chamber 80 comprises a blood outlet 82 for blood output from the inner volume 86 of the degassing chamber 80: the blood outlet 82 is connected or connectable to a fourth end 7d of the return line 7. In an embodiment, the blood outlet 82 is irremovably coupled, e.g. heat or ultrasound welded or glued, to the fourth end 7d of the return line 7. The blood outlet 82 of the degassing chamber 80 defines a blood outlet direction 82a representing the blood direction exiting the inner volume of the degassing chamber. The blood outlet direction 82a is substantially parallel to the height direction H of the degassing chamber 80.

[0348] The blood outlet 82 includes an inner surface coupled in contact with the external surface of the blood return line 7: thus, the inner surface of the blood outlet 82 and the external surface of the blood return line 7 may have substantially the same diameter. The inner surface of the blood outlet 82 has circular shape according to a cross sectional view orthogonal to the blood outlet direction 82a. Notably, given that the blood outlet 82 has cylindrical shape, the blood outlet direction 82a corresponds to a longitudinal axis of said cylindrical shape. The inner surface of the blood outlet 82 may have a diameter comprised between 8.9 mm and 4 mm, for example 6.1 mm.

[0349] Notably, the blood outlet 82 may comprise a stop portion 82c facing, and in particular contacting, a thickness wall of an end 7d of the blood return line 7: the stop portion 82c of the blood outlet 82 may be substantially orthogonal to the blood outlet access direction 82a. The thickness wall of the blood return line 7 defines a thickness of the blood return line 7 measured between an inner lumen and an external surface of the blood return line 7. The thickness of the blood return line 7 exiting the degassing chamber 80 may be comprised between 0.75 mm and 1.5 mm and more particularly between 1 mm and 1.4 mm (e.g., is equal to 1.2 mm). Correspondingly the stop portion 82c assumes corresponding ranges or value. The blood outlet 82 may include a rastered invitation (e.g., 2-4 mm long) to aid insertion of the blood tube during assembly. The rastered invitation reduces the entry hole from about 7.5 mm to about 6.4 / 6.1 mm. Downstream the stop portion 82c the inlet passage section corresponds to the lumen passage section of the blood return line 7 and for example is about 4 / 4.1 mm.

[0350] Thus, the blood return line 7 extends along a first tract 7' between the first end 7a, connected to the filtration unit 2, and the third end 7c connected to the blood inlet 81 of the degassing chamber 80. The blood return line 7 further extends along a second tract 7” between the fourth end 7d, connected to the blood outlet 82 of the degassing chamber 80, and the second end 7b for connection to the patient. Therefore, the blood return line 7 is configured to allow blood to flow from said first tract 7' to the degassing chamber 80, and from the degassing chamber 80 to said second tract 7” of the return line 7 towards the patient.

[0351] The degassing chamber 80 also comprises a fluid infusion inlet 83 connected to the first end 74a of the fluid infusion line 74 for delivering an infusion fluid, e.g. a calcium solution, in the blood flow downstream the filtration unit 2. The fluid infusion inlet 83 may be irremovably coupled to the fluid infusion line 74, e.g. heat or ultrasound weld or glue. The fluid infusion inlet 83 defines a respective infusion access direction 83a representing the fluid direction entering the inner volume of the degassing chamber.

[0352] The fluid infusion inlet 83 includes an inner surface coupled in contact with the external surface of the fluid infusion line 74: thus, the inner surface of the fluid infusion inlet 83 and the external surface of the fluid infusionP51117PC00

[0353] line 74 may have substantially the same diameter. Notably, the inner surface of the fluid infusion inlet 83 has circular shape according to a cross sectional view orthogonal to the infusion access direction 83a. Notably, given that the fluid infusion inlet 83 has cylindrical shape, the infusion access direction 83a corresponds to a longitudinal axis of said cylindrical shape. The inner surface of the fluid infusion inlet 83 may have a diameter comprised between 6.6 mm and 1.6 mm, for example 4.4 mm. The inner surface of the fluid infusion inlet 83 may be lower than the inner surface of the blood inlet 81 and of the blood outlet 82.

[0354] Notably, the fluid infusion line 74 is received inside the fluid infusion inlet, so that the external surface of the fluid infusion line contacts the inner surface of the fluid infusion inlet 83.

[0355] The blood inlet 81 may be at a distance, measured parallel to the height direction of the degassing chamber, from the fluid infusion inlet 83 of the degassing chamber 80 comprised between 6 mm and 25 mm.

[0356] The fluid infusion inlet 83 may comprise a stop portion 83c facing, and in particular contacting, a thickness wall of the first end 74a of the fluid infusion line 74: the stop portion 83c of the fluid infusion inlet 83 may extend substantially orthogonal to the infusion access direction 83a. Notably, the thickness wall of the fluid infusion line 74 is measured radially as a thickness between the inner lumen and the external surface of the fluid infusion line 74.

[0357] The thickness of the fluid infusion line 74 entering the degassing chamber 80 may be comprised between 1 mm and 2 mm and more particularly between 1.25 mm and 1.75 mm (e.g., is equal to 1.475 mm). Correspondingly the stop portion 83c assumes corresponding ranges or value. The fluid infusion inlet 83 may include a rastered invitation (e.g., 1.5-3.5 mm long) to help with the insertion of the fluid infusion tube during assembly. The rastered invitation reduces the entry hole from about 6.6 mm to about 4.6Z4.4 mm. Downstream the stop portion 83c the inlet passage section corresponds to the lumen passage section of the fluid infusion line 74 and for example is about 1.6 / 1.8 mm.

[0358] The total length of the fluid infusion inlet 83 from the entry to the main wall of the degassing chamber (where the stop portion 83c is also located in a cross section along a vertical plane) is less than 15 mm and possibly less than 10 mm.

[0359] As shown in figures 3-6, the degassing chamber 80 extends, at least during an operative condition of the degassing chamber 80, along a height direction H from a bottom portion 84 to a top portion 85. The height direction H may be defined as parallel, during an operative condition of said degassing chamber 80, to the gravitational force.

[0360] The fluid infusion inlet 83 of the degassing chamber 80 may be interposed between the blood inlet 81 and the blood outlet 82 of the degassing chamber 80 with respect to the height direction H. In detail, the degassing chamber 80 has a height measured along the height direction H comprised between 70 mm and 100 mm (e.g., about 85 mm). The height of the degassing chamber defines a main dimension of the degassing chamber 80, wherein the blood inlet 81, the blood outlet 82 and the fluid infusion inlet 83 are arranged below a midline of said height.P51117PC00

[0361] As shown in figure 6, the infusion access direction 83a may be transverse, and optionally orthogonal, to the blood outlet direction 82a. In particular, the infusion access direction 83a may or may not intersect the blood outlet direction 82a.

[0362] The fluid infusion access direction 83a may be substantially parallel to the blood inlet access direction 81a. Thus, the blood inlet access direction 81a is transversal, optionally orthogonal, to the blood outlet direction 82a. De facto, the blood inlet access direction 81a of the blood inlet 81 is transverse, optionally orthogonal, to the height direction H of extension of the degassing chamber 80. In the shown example, the blood inlet access direction 81a is horizontal during normal use of the degassing chamber. In the illustrated example, the blood outlet direction 82a is vertical during normal use of the degassing chamber.

[0363] As shown in figures 3-5, the infusion access direction 83a may be parallel to the blood inlet access direction 81a of the blood inlet 81. For example, the infusion access direction 83a may be horizontal during normal use of the degassing chamber, thus orthogonal to the height direction H.

[0364] Notably, the blood inlet 81 of the degassing chamber 80 may be tangential to the inner volume 86 of the degassing chamber 80, to generate a swirling blood movement of the blood within the inner volume 86 which improves gas removal and mixing with infusion fluids. On this regard, the inner volume 86 may have a circular cross-sectional shape orthogonal to the height direction H of the degassing chamber 80. In detail, the blood inlet access direction 81a is offset with respect to the blood outlet direction 82a by a distance lower than 30 mm, more in particular lower than 15mm and more specifically comprised between 1 mm and 14 mm, more in particular by a distance of 7.8 mm ± 2 mm. The offset between the blood inlet access direction 81a and the blood outlet direction 82a may be measured orthogonally to the height direction H.

[0365] The degassing chamber 80 may comprise an auxiliary fluid infusion inlet 91 arranged above the blood inlet 81, so that the blood inlet 81 is interposed between the fluid infusion inlet 83 and the auxiliary fluid infusion inlet 91 along the height direction H of the degassing chamber. De facto the auxiliary fluid infusion inlet 91 is interposed between the top portion 85 of the degassing chamber 80 and the blood inlet 81 along the height direction of the degassing chamber. The auxiliary fluid infusion inlet 91 may be arranged at a height level substantially corresponding to the blood level during an operative condition of the disposable set. In particular, the auxiliary fluid infusion inlet 91 may be arranged above a midline of the height of the degassing chamber, while the fluid infusion inlet 83 is arranged below said midline of the height of the degassing chamber.

[0366] The auxiliary fluid infusion inlet 91 defines an auxiliary infusion access direction 91a, representing the fluid direction entering the inner volume of the degassing chamber 80. The auxiliary infusion access direction 91a may be transverse, and optionally orthogonal, to the blood outlet direction 82a. In particular, the auxiliary infusion access direction 91a intersects the blood outlet direction 82a. De facto, the auxiliary infusion access direction 91a may be orthogonal to the height extension of the degassing chamber 80. Notably, the auxiliary infusion access direction 91a may be transversal, and optionally orthogonal, to the blood inlet access direction 81 a of the blood inlet 81. For example, the infusion access direction 91 a is horizontal during normal use of the degassing chamber.P51117PC00

[0367] The auxiliary fluid infusion inlet 91 includes an inner surface coupled in contact with the external surface of the auxiliary fluid infusion line 63: thus, the inner surface of the auxiliary fluid infusion inlet 91 and the external surface of the auxiliary fluid infusion line 63 may have substantially the same diameter. Notably, the inner surface of the fluid infusion inlet 91 has circular shape according to a cross sectional view orthogonal to the auxiliary infusion access direction 91a. Notably, given that the auxiliary fluid infusion inlet 91 has cylindrical shape, the auxiliary infusion access direction 91a corresponds to a longitudinal axis of said cylindrical shape. The degassing chamber comprises a top aperture 92 connected to a service line 93 for controlling the blood level in the inner volume of the degassing chamber during a blood treatment. The service line 93 extends between a first end 93a fluidly connected to top aperture 92 of the degassing chamber 80 and a second end 93b configured to be connected to a level controlling system 93c of the extracorporeal blood treatment apparatus 1. The level controlling system 93c of the extracorporeal blood treatment apparatus 1 is configured to control and / or vary a blood level in the degassing chamber 80.

[0368] The top aperture 92 defines a respective top aperture direction 92 of connection with the service line 93: the top aperture direction 92 may be substantially parallel to the height direction of the degassing chamber 80. In particular the top aperture direction 92 may be substantially parallel, or coincident, to the blood outlet direction 82a. Thus, the blood outlet 82 faces downwards, at least during an operating condition of the disposable set, while the top aperture 92 may face upwards.

[0369] The service line 93 may comprise an access site 93d configured to allow an operator for manually drawing fluid, in particular air, from said service line 93 or for manually sending fluid, in particular air, into the service line 93. Furthermore, the service line 93 or said top aperture 92 of the degassing chamber 80 may comprise a hydrophobic membrane 93e configured to allow passage of gas and to prevent passage of liquid. Thus, liquids that may be contained in the degassing chamber such as, blood, replacement fluid, saline cannot pass through the hydrophobic membrane 93e. The main function of the fluid barrier is to prevent the ingress of blood / fluid into the return pressure monitoring circuit within the extracorporeal blood treatment apparatus 1. Another function of the fluid barrier is to act as a sterile barrier against germs between the 'reusable' pressure monitoring circuit of the blood treatment apparatus 1 and the volume of air above the blood interface..

[0370] Notably, the blood inlet 81, the blood outlet 82, and the fluid infusion inlet 83 of the degassing chamber 80 define a solid body, e.g. wherein the blood inlet 81 , the blood outlet 82, and the fluid infusion inlet 83 are integral to each other.

[0371] As shown in figure 6, the inner volume 86 comprises a main housing 87, a mixing chamber 89 and a reduced passage 88 interposed between the main housing 87 and the mixing chamber 89, so that blood flows, during an operative condition of the disposable set, from the main housing 87, through the reduced passage 88, to the mixing chamber 89. In more detail, the blood flows from the blood inlet 81 into the main housing 87, and from the main housing 87 to the mixing chamber 89 passing through the reduced passage 88. Thus, the blood inlet 81 is in fluid communication with the main housing 87, wherein the blood inlet 81 enters the main housing 87 at a blood inlet delivery spot.P51117PC00

[0372] The main housing 87 defines the reservoir housing the blood during a blood treatment and may have circular shape according to a sectional view orthogonal to the height direction of the degassing chamber. The circular shape of the main housing 87 may have a diameter, measured at the blood inlet 81 , comprised between 15 mm and 45 mm, more specifically lower than 35 mm and / or higher than 20 mm. In one example the diameter is about 28 mm.

[0373] The main housing 87 may comprise a conical bottom portion 87a interposed between the blood outlet 82 and the blood inlet 81 along the height direction H of the degassing chamber 80, so that blood is allowed to flow from the blood inlet 81, through the conical bottom portion, and towards the blood outlet 82. The conical bottom portion 87a is interposed between the blood inlet 81 and the fluid infusion inlet 83 along the height direction H of the degassing chamber 80. Notably, the conical bottom portion 87a is part of the inner volume 86 of the degassing chamber. The conical bottom portion 87a is arranged upstream with respect to (and converges towards) the reduced passage 88 and the mixing chamber 89.

[0374] The conical bottom portion 87a defines an angle a, included within the inner volume, comprised between 70° and 80°, in particular between 74° and 78°. De facto the conical bottom portion 87a comprises a lateral wall having conical shape reducing the passage section towards the reduced passage: the angle a defines the inclination of the side wall. In other terms, the angle a has its vertex at the reduced passage 88.

[0375] The passage section for blood flow of the inner volume 86 decreases from the main housing 87 to the reduced passage 88, and then increases from the reduced passage 88 to the mixing chamber 89. De facto the reduced passage 88 defines a Venturi channel for the blood flowing from the main housing 87 to the mixing chamber 89.

[0376] The passage section of the inner volume 86, measured at the reduced passage 88, is smaller than the passage section of the inner volume measured at the mixing chamber 89. In detail, the passage section of the inner volume 86 is minimum at the reduced passage 88, which defines the minimum passage section for blood in the degassing chamber.

[0377] The passage section of the inner volume 86 measured at the reduced passage 88 may have a circular cross section. The diameter of the circular cross section of the reduced passage may be comprised between 1 mm and 2.2 mm, optionally between 1.2 mm and 2 mm, for example 1.6 mm.

[0378] The passage section of the inner volume 86 measured at the reduced passage 88 is comprised between 0,7 mm2and 4 mm2, optionally between 1.1 mm2and 3,1 mm2, more optionally between 1,6 mm2and 2,7 mm2, for example 2 mm2.

[0379] The reduced passage 88 may extend, along a direction orthogonal to the reduced passage section, by a length comprised between 0,5 mm and 10 mm, optionally between 0,7 mm and 5 mm, more optionally between 1 mm and 2 mm. In other terms, the mixing chamber 89 may be at a distance from the main housing 87 of the degassing chamber 80 comprised between 0,5 mm and 10 mm, in particular between 0,7 mm and 5 mm, more optionally between 1 mm and 2 mm.

[0380] The passage section of the inner volume 86 may increase from the reduced passage 88 to the mixing chamber 89 almost abruptly along a direction from the reduced passage 88 to the mixing chamber 89, namely along theP51117PC00

[0381] blood direction. The diameter may increase abruptly in the range 15% to 50% (of about 25%), for example from 1.6 mm to about 2 / 2.1 mm.

[0382] The mixing chamber has a first portion directly receiving the fluid from the reduced passage that is tapered. Its cross section increases moving towards the blood outlet 82. A tapering angle between the two inclined inner surfaces / lines is comprised between 15° and 30°, specifically about 22°.

[0383] The mixing chamber has a second cylindrical portion directly emerging and receiving the fluid from the first portion. The second portion ending in correspondence of the stop portion 82c of the blood outlet 82.

[0384] The reduced passage 88 defines a reduced passage axis RPA representing the blood direction flowing through: the reduced passage axis RPA may be orthogonal to the infusion access direction 83a of the fluid infusion inlet 83. De facto, the reduced passage axis RPA of the reduced passage 88 is representative of a flow direction of the blood from the main housing 87 to the mixing chamber 89, and it may be parallel to the height direction of the degassing chamber 80. Furthermore, the reduced passage axis RPA may be parallel, and optionally coincident, to the blood outlet direction 82a. The first portion extend in height along the reduced passage axis RPA for more than 1.5 mm and less than 5.4 mm. The tapering angle of the mixing chamber 89 with respect to the reduced passage axis RPA is between 10° and 15°, for example about 11 °.

[0385] The second cylindrical portion of the mixing chamber extending in height along the reduced passage axis RPA for more than 2 mm and preferably less than 4 mm.

[0386] The mixing chamber 89 is interposed between the reduced passage 88 and the blood outlet 82, so that the blood flows from the reduced passage 88 into the mixing chamber 89, and from the mixing chamber 89 to the blood outlet 82. Thus, the mixing chamber is arranged downstream with respect to the reduced passage 88 and upstream with respect to the blood outlet according to a blood flow direction during a standard operating condition of the disposable set.

[0387] Notably, the mixing chamber 89 defines a blood passage section greater than the one defined at the reduced passage. Thus, the passage section for blood flow of the inner volume 86 decreases from the main housing 87 to the reduced passage 88, and then increases from the reduced passage 88 to the mixing chamber 89. The mixing chamber 89 defines a cross section, orthogonal to a direction from the main housing 87 to the mixing chamber 89, having circular shape. A maximum diameter of the circular shape of the cross section of the mixing chamber may be comprised between 3 mm and 5 mm, optionally between 2,6 mm and 4,4 mm: in particular, the maximum diameter of the circular shape of the cross section of the mixing chamber may be comprised between 4 mm and 4,2 mm. The maximum diameter is the diameter of the second cylindrical portion.

[0388] A length of the mixing chamber measured between the reduced passage 88 and the fourth end 7d of the blood return line is comprised between 4 mm and 7 mm, optionally between 5 mm and 6 mm. In particular, said length may be substantially equal to 5.4 mm ± 0.2 mm.

[0389] The fluid infusion inlet 83 is connected to the mixing chamber, so that the infusion fluid, e.g. a calcium liquid solution, flows from the fluid infusion line 74 into the fluid infusion inlet 83, and from the fluid infusion inlet 83 into the mixing chamber 89.P51117PC00

[0390] In particular, the fluid infusion inlet 83 comprises a nozzle 90 flowing into the mixing chamber 89, so that the nozzle 90 of the fluid infusion inlet 83 is configured to deliver infusion fluid directly into the mixing chamber 89, in particular in correspondence of a lateral wall of the first (tapered) portion. The nozzle 90 of the fluid infusion inlet 83 has a fluid passage section that decreases in size in the direction of the fluid infusion, namely along a direction from the first end 74a of the fluid infusion line 74 towards the mixing chamber of the degassing chamber 80. The nozzle 90 may have a tronco-conical shape. A cross section of the nozzle 90, defined orthogonal to the fluid infusion direction, is minimum at the entry into the mixing chamber 89: in particular, the minimum cross section of the nozzle 90 may have a diameter comprised between 0.5 and 1.2 mm. Notably, a minimum diameter of the nozzle 90 may be smaller than a minimum diameter of the reduced passage 88.

[0391] Notably, a distance between a central axis of the nozzle 90 of the fluid infusion inlet 83 and the blood inlet access direction 81 a of the blood inlet 81 is comprised between 10 mm and 30 mm, more in particular between 14 mm and 22 mm, for example 18.5 mm ± 1 mm. This distance is measured parallel to the height direction H of the degassing chamber 80.

[0392] Analogously, given that the fluid infusion inlet 83 enters the mixing chamber 89 at an infusion inlet delivery spot 83b for delivering fluid in the mixing chamber 89, the blood inlet access direction 81a may be spaced from the central axis of the nozzle 90 in a horizontal plane by a distance comprised between 4 mm and 12 mm, more in particular between 6 mm and 10 mm, more in particular by a distance of 7.8 mm ± 0.5 mm.

[0393] The main housing 87, the mixing chamber 89 and the reduced passage 88 define together a solid body. In detail, the main housing 87, the mixing chamber 89 and the reduced passage 88 are integral to each other being made in one-piece and seamlessly joined together.

[0394] The degassing chamber 80 may be made in two pieces, wherein a first body 80a and a second body 80b are coupled to each other defining the degassing chamber 80 in one piece. The first body 80a may be made in one piece by plastic molding: analogously, the second body 80b may be made, separately by the first body 80a, in one piece by plastic molding. After the molding process, the first body and the second body are coupled together by a welding process or glue.

[0395] The first body 80a may include the blood inlet 81, the blood outlet 82 and the fluid infusion inlet 83, while the second body 80b may include the auxiliary fluid infusion inlet 91. According to this arrangement, the first body 80a may be arranged below the to the second body 80b along the height direction H of the degassing chamber 80 during an operating condition of the disposable set, namely during a blood treatment.

[0396] The degassing chamber 80 may also include a fluid deviator 94, shown in figures 7 and 8, positioned in the inner volume 86 of the degassing chamber 80. The fluid deviator 94 delimits, within the inner volume 86, an annular chamber configured to allow fluid and / or blood to flow towards the blood outlet 82 of the degassing chamber 80. The fluid deviator 94 has a cross section, defined along a plane orthogonal to the height direction H, having circular shape, wherein a diameter of the cross section of the fluid deviator 94 may vary along the height direction H. In detail, the diameter of the cross section of the fluid deviator 94 may vary along the height direction H according to a curved profile, e.g. according to a semicircular profile as shown in figure 8.P51117PC00

[0397] The fluid deviator 94 comprises an external surface 94a having concave shape, wherein the external surface 94a faces the blood inlet 81 of the degassing chamber 80. The external surface 94a may also face the auxiliary fluid infusion inlet 91 of the degassing chamber 80.

[0398] The fluid deviator 94 may comprise an extremal portion 95 having conical shape facing the conical bottom portion 87a of the main housing 87 of the degassing chamber.

[0399] Notably, the fluid deviator 94 is positioned in the main housing 87 of the degassing chamber, thereby upstream the reduced passage 88 of the degassing chamber.

[0400] Pulsed calcium infusion and pressure valve on the fluid infusion line

[0401] According to an embodiment shown in figures 1, 2 and in figures from 9 to 16, the disposable set 100 may comprise a pressure valve 76 configured to perform a pulsed infusion of the infusion fluid in the blood circuit 17. Notably, as already pointed out previously, it is desirable to allow adequate mixing between the blood, carried by the return line 7, and the infusion fluid, e.g. the calcium solution carried by the infusion line 74 and contained in the infusion substance source 11. The above-mentioned pulsed infusion allows improving the mixing between the two liquids. Indeed, a discontinuous calcium infusion process can prevent thrombus formation at the infusion site. Notably, a pulsed infusion defines an alternating infusion, in terms of flow rate “Q”, over time “t” of the infusion fluid in the blood circuit, wherein high flow rates of the infusion fluid (namely the pulses) are alternated with time intervals wherein the infusion rate Q of the infusion fluid is null or strongly reduced.

[0402] From an overall perspective, calcium infusion rate is defined by:

[0403] - the hourly amount of calcium to be delivered (Jca in mmol / h) from a therapy perspective;

[0404] - a (mean) infusion flow rate Qca set for the calcium infusion device, which is dependent on the concentration of the calcium solution ([Ca]soi).

[0405] >

[0406]

[0407] When introducing a discontinuous and periodical infusion process, following additional parameters are introduced:

[0408] - the bolus period Tboius at which calcium boluses are delivered,

[0409] - a dimensionless factor a representing the fraction of time calcium is infused, or the ratio between instantaneous flow Qinf and average flow Qca.

[0410] T Qca

[0411] a = - - = 6 [0; 1]

[0412] ‘bolus Qinf

[0413] Figure 13 schematically shows a pressure profile expected in the case of a simple valve opening and closing. It represents an exemplary trend of the flow rate Q in the infusion line 74 over time t, wherein the flow rate Q varies between a reduced or null flow rate and a maximum flow rate Qmax. The bolus period Tboius between twoP51117PC00

[0414] successive calcium boluses is shown as well as the average calcium flow rate Qinf which is the mean flow rate during the opening phase of the valve during the infusion. T represents the time duration of the single bolus. The total volume of infusion fluid that is infused for each bolus is represented by Qinf times the bolus infusion time T and corresponds to the area below the single pulse.

[0415] Figure 14 shows the pressure regimen P within the infusion line 74 upstream of the pressure valve 76 and downstream of the pump 75. On the left of the diagram, the infusion pump 75 is pumping at a constant rate Qcawhile the pressure valve 76 is closed. When the pressure in the infusion line 74 reaches the opening pressure P2, the valve 76 opens and the infusion fluid is discharged. During the fluid discharge (i.e., during the bolus infusion), the pressure inside the infusion line decreases to the closure pressure P2 (when the bolus infusion ends). Meanwhile, the infusion pump 75 continues to pump at the same rate Qca. Therefore, after the pressure valve closes, the pressure in the infusion line begins to rise again until the pressure again reaches the opening pressure P2 and another bolus is injected. The cycle is repeated to provide the pulsed infusion.

[0416] Note that different pressure valves may result in different pressure / infusion profiles.

[0417] When operating with continuous calcium infusion (a = 1), clotting problems are sometimes expected.

[0418] Clearly, excessively long infusion periods without calcium infusion are not acceptable as creating a risk of periodic hypocalcaemia for the patient. An upper limit of 15-20 minutes looks reasonable in this respect for the (Tboius-T) time which implies:

[0419]

[0420] On the other side, high values of parameter a are at risk of clotting as similar to the continuous infusion process. An upper value of 0.5 will be considered reasonable for the parameter a.

[0421] At the same time, very short infusion times are also expected to reproduce the clotting problems associated with continuous infusion due to the time constant of the hydraulic circuit for renewal and cleaning of the boundary layer where calcium is present in excessive concentration. Consequently, bolus times below 5-10 s are not considered significant.

[0422] In addition, very short infusion times (T below 1 second) appears impractical and difficult to perform. This condition matches with the following relation:

[0423]

[0424] Figure 17 shows an illustration of the operating range of potential interest for periodic calcium bolus infusion combining all the above-described constraints.

[0425] Returning now to the diagram of figure 13, the continuous line represents a theoretical trend of the flow rate Q over time t, while the dotted line may represent an actual or experimental trend of the flow rate Q over time. InP51117PC00

[0426] detail, said flow rate Q of the infusion fluid is measured at the first end 7a of the infusion line 74, namely where the infusion fluid enters the blood circuit 17.

[0427] The pressure valve 76 allows obtaining said pulsed infusion, even if the infusion pump 75 is running at a set speed, e.g. a constant speed. De facto, the pressure valve 76 defines a passive device, namely not electronically commanded and controllable by a control unit, able to define passively the desired pulsed infusion. The pressure valve 76 may be interposed along the fluid infusion line 74 between the pump tract 74p of the infusion line 74, configured to engage the infusion pump 75, and the first end 74a of the fluid infusion line 74 connected to the blood circuit. Analogously, the pump tract 74p is interposed along the fluid infusion line 74 between the pressure valve 76 and the second end 74b of the fluid infusion line 74. De facto, the pump tract 74p of the fluid infusion line 74 is upstream with respect to the pressure valve 76 along the infusion line 74. The pressure valve 76 may be located on the infusion line 74 close to the first end 74a of the infusion line 74, e.g. at a maximum distance from the first end 7a of the fluid infusion line 74 less than 100 mm, optionally less than 50 mm or 25 mm, optionally comprised between 5 mm and 100 mm.

[0428] The pressure valve 76 is movable between a flow position and an interception position: in particular, the pressure valve 76 is configured to switch from the interception position to the flow position when a differential pressure across the pressure valve 76 exceeds an aperture pressure P1, and to switch back from the flow position to the interception position when the differential pressure across the pressure valve 76 falls below a closure pressure P2. Notably, the closure pressure P2 is different and below the aperture pressure P1. The aperture pressure P1 may be comprised between 0.5 bar and 5 bar, while the closure pressure P2 may be comprised between 0 bar and 0.5 bar. The aperture pressure P1 may be at least 50% greater than the closure pressure P2. In detail, a pressure difference between the aperture pressure P1 and the closure pressure P2 is comprised between 0.5 bar and 4 bar.

[0429] The pressure valve 76, after switching from the interception position to the flow position, is then configured to maintain the flow position as long as the differential pressure is greater than the closure pressure P2. Differently, the pressure valve 76, when in the interception position, is configured to maintain the interception position up to the aperture pressure P1. In other terms, starting from a condition wherein the pressure valve 76 is in the interception position, as the differential pressure increases and exceeds the aperture pressure P1 , the pressure valve 76 opens in the flow position: then, as the pressure decreases, the pressure valve 76 maintains the flow position as long as the differential pressure is greater than the closure pressure P2. As soon as the differential pressure falls below the closure pressure, the pressure valve 76 closes in the interception position.

[0430] Notably, the differential pressure is defined between a valve inlet of the pressure valve 76 and a valve outlet of the pressure valve 76. The valve inlet faces an upstream tract of the fluid infusion line 74 towards the second end 74b of the fluid infusion line 74, while the valve outlet faces a downstream tract of the fluid infusion line 74 towards the first end 74a of the fluid infusion line 74. Thus, the pressure valve 76 is configured to switch from the interception position to the flow position when a fluid pressure at the valve inlet is higher than a fluid pressure at the valve outlet by at least the above-mentioned differential pressure. De facto, the differential pressure is the difference between the fluid pressure at the valve inlet and the fluid pressure at the valve outlet.P51117PC00

[0431] Notably, the pressure valve 76, when arranged in the flow position, is configured to allow a fluid flow in the fluid infusion line 74 from the second end 74b to the first end 74a of the fluid infusion line 74. On the contrary, the pressure valve 76, when arranged in the interception position, is configured for preventing, or reducing with respect to the flow position, a fluid flow in the fluid infusion line 74 from the second end 74b to the first end 74a of the fluid infusion line 74. Thus, in the interception position, the pressure valve may completely stop the fluid flow along the fluid infusion line from the second end 74b to the first end 74a, or allow a small flow rate, (much) lower than in the flow position, of infusion fluid to pass through. De facto, the pressure valve in the flow position allows a fluid flow greater than in the interception position. The pressure valve in the interception position defines a maximum closure of the pressure valve.

[0432] The pressure valve 76 defines internally a fluid passage cross section to allow the infusion fluid to flow from the second end 74b to the first end 74a of the infusion line 74. Thus, the fluid passage cross section of the pressure valve is variable in size between the interception position and the flow position. When the pressure valve 76 switches from the interception position to the flow position, the fluid passage cross section moves from a minimal or zero fluid passage cross section Smin of the interception position, to a maximum fluid passage cross section Smax of the flow position. Accordingly, figure 15 shows the trend of the fluid passage cross section S of the pressure valve 76 as a function of the differential pressure P across the pressure valve 76. The fluid passage cross section of the pressure valve 76 is maximum at the instant the pressure valve 76 switches from the interception position to the flow position. In other terms, the maximum aperture of the pressure valve 76 is defined when the fluid passage cross section corresponds to the maximum fluid passage cross section Smax. On the contrary, the minimal or zero fluid passage cross section corresponds to a maximum closing passage section of the pressure valve 76. A zero fluid passage cross section Smin defines a closed fluid passage. The fact that the pressure valve 76, when the differential pressure crosses and exceeds the aperture pressure P1 , switches from the minimal or zero fluid passage cross section Smin of the interception position to the maximum fluid passage cross section Smax indicates that the fluid passage cross section increases very quickly, almost instantaneously, de facto defining an instability between the interception position and the flow position when the differential pressure crosses and exceeds the aperture pressure P1. This behavior of the pressure valve 76 allows the pulsed infusion to be performed. Indeed, with the pressure valve 76 in the interception position, the pressure in the upstream tract of the infusion line 74 increases over time as the infusion pump 75 keeps running, eventually exceeding the aperture pressure P1 : when the differential pressure P exceeds the aperture pressure P1, the pressure valve 76 completely opens defining the maximum fluid passage cross section, allowing the fluid under pressure contained in the upstream tract of the infusion line 74 to be delivered towards the first end 74a of the infusion line 74, entering the blood circuit as a fluid pulse. As the infusion fluid flows through the pressure valve, the differential pressure reduces accordingly until it drops below the closure pressure P2, thereby triggering the switch of the pressure valve in the interception position. The pulsed infusion improves the mixing between the infusion fluid and the blood circulating in the blood circuit.P51117PC00

[0433] Notably, the infusion line 74 comprises an inner lumen having a respective fluid passage cross section. A ratio between the fluid passage cross section of the fluid infusion line 74 and the maximum fluid passage cross section Smax of the pressure valve 76 may be comprised between 0,7 and 1,3, optionally between 0,85 and 1.2, optionally between 1 and 1,2.

[0434] The pressure valve 76 may be a duckbill valve, not shown in the attached figures. Alternatively, the pressure valve may be a cross-cut valve or a cross-slit valve as shown in figures 9-11. Notably, the pressure valve 76 is not a check valve. The pressure valve 76 may comprise a dome-shaped or hemispherical diaphragm 78, at least when arranged in the interception position, as clearly shown in the cross-section view of figure 10. The diaphragm 78 includes at least one through cut 77 configured to selectively allow and prevent fluid flow. In particular, when the pressure valve 76 is in the interception position, the through cut 77 is closed to prevent or reduce fluid flow in the fluid infusion line 74, and when the pressure valve 76 is in the flow position, the through cut is open to allow fluid flow in the fluid infusion line 74. Notably, the dome-shaped or hemispherical diaphragm deforms, and optionally inverts its concavity, when the pressure valve switches between the flow position and the interception position. The dome-shaped or hemispherical diaphragm defines a convex side 76a and a concave side 76b, as shown in figure 10. When the pressure valve 76 is in the interception position, the convex side 76a faces the upstream tract of the fluid infusion line 74 and the concave side 76b faces the downstream side of the fluid infusion line 74, as shown in figure 12. If the dome-shaped or hemispherical diaphragm 78 inverts its concavity when switching from the interception position to the flow position, then in the flow position the convex side 76a faces the downstream tract of the fluid infusion line 74 and the concave side 76b faces the upstream side of the fluid infusion line 74.

[0435] The diaphragm 78 may comprise a first through cut and a second through cut crossing each other, optionally orthogonally, as shown in figures 9 and 11. The first through cut may intersect the second through cut at a midpoint of the second through cut, and the second through cut may intersect the first through cut at a midpoint of the first through cut, thereby defining a crosscut.

[0436] The pressure valve 76 may be in one piece and made of a silicone or rubber or plastic material.

[0437] In the embodiment comprising the pressure valve 76, the fluid infusion line 74, and in particular the tract of the fluid infusion line 74 between said pressure valve (76) and the pump tract (74p) of the fluid infusion line (74), defines a compliant circuit section.

[0438] In a first example, the compliant circuit portion is defined by a compliant tube made of a flexible elastic material such as silicone or PVC. The deformability or stretch ability of the circuit portion of the fluid infusion line 74 helps to enable the pulsed infusion to be performed. As the pressure in this portion of the infusion line 74 increases due to the activation of the infusion pump 75, the internal volume of the infusion line 74 increases accordingly, thereby increasing the pressure and the volume of fluid contained therein. When the pressure valve 76 switches to the flow position, as soon as the differential pressure exceeds the opening pressure P1 , the infusion fluid is released through the pressure valve 76 towards the blood circuit. As the infusion fluid flows through the pressure valve 76, the pressure in the upstream portion of the infusion line 74 decreases until it falls below the closingP51117PC00

[0439] pressure P2. For example, the compliant tube may have an internal volume that increases between 0.5 ml and 2 ml for each 1 bar increase in pressure.

[0440] Alternatively, or in combination, the compliance of the circuit section may be provided by the use of a compliant chamber 96 located along the tract. The chamber may, for example, have an upper portion occupied by air which provides compliance to the section between the pump 75 and the valve 76. Also, the chamber 96 may be in the form of a bubble trap.

[0441] In another embodiment, the chamber may be resilient so that it undergoes a deformation induced by the increase in pressure which increases its fluid containment volume.

[0442] Obviously, both of the technical solutions described above can be implemented, i.e. pipe compliance plus chamber 96.

[0443] In a rest condition, wherein no pressure is applied inside the infusion line 74, the upstream tract of the fluid infusion line 74 defines an inner volume configured to house fluid. This inner volume is measured between the pressure valve 76 and the pump tract 74p of the fluid infusion line 74. This inner volume may be comprised between 1 ml and 10 ml.

[0444] In the embodiment comprising the pressure valve 76, the first end 74a of the infusion line 74 may be connected to the return line 7 of the blood circuit, or to the degassing chamber 80. In more detail, if the first end 74a of the infusion line 74 is connected to the return line 7 of the blood circuit 17 as shown in figure 16, the first end 74a of the infusion line 74 may be located downstream the degassing chamber 80. The blood return line 7 may include a 3-way connector, or a “T” connector, comprising a blood inlet connected to an upstream tract of the blood return line 7, a blood outlet connected to a downstream tract of the blood return line 7, and an infusion inlet connected to the first end 7a of the fluid infusion line 74. The upstream tract of the blood return line 7 is interposed between the degassing chamber 80 and the connector, while the downstream tract is interposed between the connector and the second end 7b of the return line 7.

[0445] On the contrary, according to the embodiment wherein the first end 74a of the infusion line 74 is connected to the degassing chamber 80 as shown in figures 1 and 2, the first end 74a of the infusion line 74 is connected to the fluid infusion inlet 83 of the degassing chamber 80.

[0446] In the embodiment comprising the pressure valve 76, the infusion substance source 11 may comprise a calcium solution source or a calcium solution bag containing or configured to contain a calcium solution fluid.

[0447] Notably, when the disposable set comprises the pressure valve 76, the control unit may be configured to perform a pulsed infusion procedure. The pulsed infusion procedure comprises a step to run the infusion pump 75 at a set speed to deliver fluid through the pressure valve 76. During an operating condition wherein the infusion pump 75 runs at the set speed, the pressure valve 76 is configured to deliver fluid towards the first end 74a of the fluid infusion line 74 intermittently over time, de facto defining a pulsed infusion, although the infusion pump runs at the set speed. Notably, the set speed of the infusion pump 75 may be a constant speed over time. Figure 14 clearly shows that the flow rate Q of the infusion fluid within the infusion line 74 varies over time t, due to the presence of the pressure valve 76, that makes the infusion pulsed even if the infusion pump 75 runs at constant speed.P51117PC00

[0448] Extracorporeal blood treatment apparatus 1

[0449] With reference to figure 1, the numeral 1 globally refers to the extracorporeal blood treatment apparatus, in particular for intensive care therapies, configured to receive the disposable set previously described. The extracorporeal blood treatment apparatus 1 is designed for performing any one of treatments like e.g., CO2 removal, blood oxygenation, TPE, hemoperfusion, dialysis treatment including any one of hemodialysis, hemofiltration, hemodiafiltration, and ultrafiltration.

[0450] The apparatus according to figure 1 is particularly designed for continuous renal replacement therapies (CRRT). CRRT systems are configured for delivering very specific treatments designed for patients versing in acute states of illness and who have temporarily lost their kidney function in its entirety. In this respect, CRRT systems may be structurally and / or operationally different from extracorporeal blood treatment systems designed for chronic patient care. In contrast to chronic patients, acute patients temporarily experience complete loss of their kidney function typically due to a contemporaneous state of severe injury or during recovery from surgery. Consequently, acute patients are often extremely weak and typically not in a condition to be submitted to regular dialysis treatment, which may further deteriorate their state and lead to serious and possibly life-threatening complications. Under circumstances as described, CRRT systems are designed to individually treat a patient exhibiting very poor health, without inducing further stress to the patient body, in particular without allowing vital parameters pertaining to the patient's blood to deviate from ideal or near-ideal values. Within the scope of this document CRRT systems are, thus, inherently characterized by one or more of the following features. CRRT involves renal replacement therapy, meaning an adjuvant therapy aimed firstly at facilitating continuous fluid removal in diuretic-resistant or acute renal failure patients. Therefore, CRRT systems inherently require a continuous net fluid removal from the patient. In other words, a CRRT system requires a fluid balance control system, such as a weight loss control system, configured to generate a continuous net weight loss rate (as opposed to merely controlling parameters to enable achieving a desired target weight loss as typically found in chronic patient care). Furthermore, acute patients experience extravascular fluid overload, which cannot be safely removed within a short period of time (e.g. within a few hours of chronic treatment) without causing potentially severe consequences (e.g. hypovolemic shock, arrhythmia, hypoxemia, hypoventilation, etc.). Therefore, a CRRT system must inherently include a much more accurate control over system parameters, in particular flow rates, in order to ensure that the required low flow rates of both blood circulating extra-corporeal ly and of treatment fluid (infused in the extracorporeal circuit or diffused through the dialyzer) are used. Moreover, CRRT treatment is performed continuously (e.g. for days or even weeks, without interruption / with minimal interruptions e.g., downtimes to change bags). Therefore, treatment settings in CRRT are based on flow rate settings, rather than settings pertaining to some specified treatment time (which would be unknown as acute patients may require treatment for an unknown time). Consequently, operation of CRRT systems cannot be based on some pre-defined absolute weight loss to be achieved, but rather on a meticulously controlled fluid balance in the patient, requiring continuous adjustments to a number of operating parameters, which have toP51117PC00

[0451] be controlled and maintained during the entire (and a priori unknown) treatment time, based on a set weightloss rate. Additionally, CRRT renal replacement therapy involves therapy substituting kidney functions for a relatively long time period and, thus, a CRRT system further requires at least either fresh dialysis liquid exchange in the dialyzer (in order to remove unwanted substances from blood and to add desired substances to the blood by diffusion) and / or fresh infusion fluid in combination with ultrafiltration (in order to remove unwanted substances from blood and to add desired substances to the blood by convection).

[0452] At least for the reasons set forth above, CRRT systems need to exhibit specific technical features enabling the system to:

[0453] - allow setting of a weight loss rate,

[0454] - continuously remove excess water in accordance with a set weight loss rate,

[0455] - operate continuously at comparably low flow rates compatible with CRRT, and

[0456] - balance ion equilibrium by means of proper dialysis being performed and / or by means of substitution fluid continuously being delivered at controlled flow rates.

[0457] Finally, in order to set up a CRRT apparatus as soon as possible, the CRRT machine is dressed using the integrated disposable set 100, wherein all the lines and the filtration unit are grouped together and already properly connected in the disposable set. Further, all the fluids are contained in pre-packaged bags (dialysis fluid or replacement fluids in bags of e.g., 2, 5 or 10 litres each) or pre-packaged syringes (heparin and / or concentrated calcium replacement solution).

[0458] The apparatus 1 of figure 1 has the extracorporeal blood circuit 17 previously described, which takes blood from a patient P, for instance through a needle or a catheter or an implanted port or other access device (not shown), introduced into a vein or artery of said patient, and through the blood withdrawal line 6 takes said blood, for instance continuously, to the filtration unit 2.

[0459] The blood passes through the primary chamber 3 of the filtration unit 2 and, through the blood return line 7, the treated blood is carried back to the patient. In the example of figure 1, the connection with the infusion line 51 is provided immediately downstream from the blood collecting zone on the blood withdrawal line 6. Specifically, the machine is equipped with the infusion substance source 10, containing an infusion fluid comprising for example a regional anticoagulant solution (e.g., citrate and / or citric acid); by using the infusion pump 54, for instance a peristaltic pump, it is possible to control the fluid flow within said (pre-blood pump or PBP) infusion line 51 by introducing the infusion fluid directly into the blood with a direct connection to the blood withdrawal line 6. As previously indicated, the direction of fluid (blood) circulation 200 during normal use of the apparatus is from the blood withdrawal line 6 towards the filtration unit 2 and from the latter through the blood return line 7 towards the patient P. A known blood pressure sensor 48 may be arranged immediately downstream the infusion line 51, namely between the infusion line 51 and the blood pump 21. The apparatus comprises the blood pump 21 for controlling and managing the suitable blood flow Qb in the circuit. The blood pump 21 is generally a peristaltic pump acting either on the blood withdrawal line (as shown e.g. in figure 1) or, alternatively, on the blood return line. An operator enters a set value for the blood flow rate Qb through a user interface 15 and a control unit 12, during treatment, is configured to control the blood pump based on the set blood flow rate.P51117PC00

[0460] Note that, alternatively, the blood pump 21 may be automatically controlled with no need of user input / prescription: in that case control unit 12 may control the blood pump 21 at a prefixed flow rate or at a flow rate calculated based on other parameters such as, for instance, other flow rates and constraints set by the medical operator or based on pressure; for instance the control unit 12 may be designed to drive the blood pump in a manner to keep the pressure detected by pressure sensor 48 within a prefixed range, or below a prefixed threshold.

[0461] Another pressure sensor 49 may be provided on the blood withdrawal line 6 for controlling the correct pressure within the blood circuit: the pressure sensor 49 is interposed between the blood pump 21 and the filtration unit 2.

[0462] After passing through the primary chamber 3 of the filtration unit 2, where the suitable exchanges of substances, molecules and fluids occur by means of a semipermeable membrane, the treated blood enters the blood return line 7, first passing through the gas exchanger 96 (if present) and the degassing chamber 80 designed so as to ensure the collection and removal of air bubbles present in the blood. The treated blood getting out of the degassing chamber 80, before being returned to the patient P passes through an air bubble sensor 55 verifying the absence of said air formations within the treated blood that has to be re-introduced in the patient's blood circulation.

[0463] In particular, the infusion line 74 is designed to infuse the infusion fluid upstream of the air bubble sensor 55 (see Figures 1, 2 and 16). This adds a safety feature to the apparatus as any potentially dangerous infusion of air into the extracorporeal blood circuit can be detected by the air bubble sensor 55 located downstream along the blood circulation direction.

[0464] Immediately downstream from the bubble sensor 55, the safety valve 20 (or venous clamp) is placed which, in case of alarm, may block the blood flow towards the patient. In particular, should the bubble sensor 55 detect the presence of air in the blood flow, the machine through safety valve 20 would be able to block immediately the passage of blood so as to avoid any consequence to the patient. A corresponding safety valve 27 (or arterial clamp) may be present on the blood withdrawal line close the patient vascular access to fully isolate the patient from the extracorporeal blood circuit in case of need. Downstream from the safety valve 20, the treated blood is then carried back to the patient P undergoing therapy.

[0465] As previously indicated, the supply line 8 includes actuator / s for conveying fluid such as the dialysis fluid pump 25 (in the embodiment of figure 1 a peristaltic pump) for controlling the flow rate Qdiai of dialysis liquid from the bag and for defining a direction 300 of dialysis fluid circulation.

[0466] After passing through the treatment unit 101, the dialysis fluid then gets into the effluent line 13 and passes through a suitable effluent pressure sensor 60. An actuator is provided for conveying fluid, for instance a dialysate pump 26 controlling the flow rate Qeff in the effluent line 13 within the fluid circuit. Also said pump will generally be a peristaltic pump. The fluid to be eliminated then passes through the blood detector 61 and is conveyed into a collection container or bag 62.

[0467] The further infusion line 63 feeds fluid into the blood return line 7 of the blood circuit 17 from the auxiliary container 64 through actuator / s for conveying fluid, generally an infusion pump 65 (in the example a peristalticP51117PC00

[0468] pump) controlling its flow rate Qrep- total replacement flow rate. In particular, the infusion liquid may be introduced directly into the degassing chamber 80. As can also be inferred, the infusion branch 58 of the dialysis fluid circuit and the infusion line 63 are equipped with a common end length 66 letting fluid to enter the blood circuit 17. Said intake end length 66 is placed downstream from the infusion pump 65 with respect to a direction of infusion and carries the fluid directly into the degassing chamber 80.

[0469] The embodiment of figure 2 differs from the embodiment of figure 1 because the fluid infusion line 74 directs the fluid to a tract in common with the auxiliary fluid infusion line 63. As visible, both infusion lines 74, 63 enters the degassing chamber 80 at the same fluid infusion inlet 83 located between the blood inlet 81 and the blood outlet 82.

[0470] The apparatus may be equipped with scales 71 for determining at least the weight of the container 14 and / or of the auxiliary fluid container 64 and / or of the infusion substance source 10 and / or of the collection container 62. In particular, said scales 71 comprises weight sensors, for instance respective scales A, B, C, D and E (for example at least an independent sensor for each fluid bag associated to the machine). In particular, there will be at least four of said scales, each being independent from the other, and each one measuring the respective weight of a bag. It should then be pointed out that there is a control unit or CPU 12 active (at least) on the blood circuit 17 and in particular active on the pressure sensor 48 for reading pressure values, on the blood pump 21, on the gas exchanger, on the other pressure sensor 49, and on the device for detecting the presence of air bubbles 55 and on the respective safety valves 20, 27. The control unit 12 has also to control the dialysis fluid circuit and, in particular, shall be input with the data detected by the scales A, B, C, D and (possibly) E and, concerning the weight of the bag 14, and shall act on the pump 25, on the selector 59, on the pressure sensor 60, then on the dialysate pump 26 and shall eventually receive the data detected by the scale A whose function is to determine the weight of the collection container 62. The control unit 12 shall also act on the auxiliary fluid infusion line 63 checking the weight of the auxiliary container 64 (checked by the scale C) and will be able to control both the infusion pump 5465 and the other selector 70. The control unit 12 shall also act on the infusion line 51 detecting the weight of the infusion substance source 10 through the scale B and suitably controlling the infusion pump 54 according to the treatments to be carried out as below detailed and explained.

[0471] The apparatus of figure 1 may be alternatively (or additionally) provided with a systemic anticoagulation system, such as a syringe pump 9 for injecting heparin downstream the blood pump 21.

[0472] The control unit 12 is also connected to a memory and to user interface, for instance a graphic user interface, which receives operator's inputs and displays the apparatus outputs. For instance, the graphic user interface may include a touch screen, a display screen and / or hard keys for entering user's inputs or a combination thereof.

[0473] The control unit 12 is also connected to the blood pump 21 and configured to control the blood pump 21 to determine a blood flow rate in the blood withdrawal line 6. During an operating condition of the extracorporeal blood treatment, the control unit is configured to define a treatment condition wherein the blood pump 21 is set at a flow rate comprised between 50 ml / min and 600 ml / min, in particular between 100 ml / min and 350 ml / min, more in particular between 120 ml / min and 200 ml / min. Of course, the blood flow rate is set by the physicianP51117PC00

[0474] and may vary depending on various factors including the vascular access, the patient conditions, and the type of treatment.

[0475] On the other hand, the infusion pump 54 is operatively connected to the control unit 12 which is configured to selectively control the infusion pump 54 to promote the infusion fluid to flow within the infusion line 51 and to deliver the infusion fluid into the blood withdrawal line 6: the control unit 12 may be configured to control the infusion pump 54 to set the flow rate of the infusion fluid typically between 200 ml / h and 4000 ml / h, in particular between 500 ml / h and 2000 ml / h. Also in this regard, the type of treatment, the infusion bag content, and other conditions determine the set infusion rate, which is however normally set in the above discussed ranges. The infusion pump 75 has a working range up to 200 ml / h. When in use is for example set at a speed defining a flow rate in the infusion line comprised between 2 ml / h and 200 ml / h (for example in a range between 3 ml / h and 50 ml / h).

[0476] Of course, the infusion flow rate depends on the calcium concentration (e.g., 50-500 mmol / L, optionally 200-400 mmol / L), the blood flow rate (e.g., 100-200 ml / min) and the amount of calcium removed by the dialyzer. Therefore, the mentioned flow rate values are just indicative.

Claims

P51117PC00CLAIMS1. Extracorporeal blood treatment apparatus (1) comprising a disposable set (100), the disposable set (100) comprising:a blood circuit (17) comprising:o a blood withdrawal line (6) extending between a first end (6a) connected or connectable to a treatment unit (101) and a second end (6b) for connection to a patient,o a blood return line (7) extending between a first end (7a) connected or connectable to the treatment unit (101) and a second end (7b) for connection to the patient;a fluid infusion line (74) extending between a first end (74a) connected to the blood circuit (17) and a second end (74b) for connection to an infusion substance source (11) configured to contain an infusion fluid, a pressure valve (76) located on the fluid infusion line (74) and interposed between the first end (74a) and the second end (74b) of the fluid infusion line (74), the pressure valve (76) being movable between a flow position and an interception position, wherein the pressure valve (76) is configured to switch:o from the interception position to the flow position when a differential pressure across the pressure valve (76) exceeds an aperture pressure (P1); ando from the flow position to the interception position when said differential pressure across the pressure valve (76) falls below a closure pressure (P2);wherein the closure pressure (P2) is below the aperture pressure (P1),wherein the extracorporeal blood treatment apparatus (1) comprises:a blood pump (21) configured to engage a respective blood pump tract (6p) of the blood withdrawal line (6);an infusion pump (75) configured to engage a respective pump tract (74p) of the fluid infusion line (74); a control unit (12) operatively connected to the blood pump (21) and the infusion pump (75), said control unit (12) being configured to perform a pulsed infusion procedure comprising a step to run the infusion pump (75) at a set speed to deliver fluid through said pressure valve (76), wherein said set speed of the infusion pump (75) is a constant speed defining a substantially constant flow rate (Qca) in the fluid infusion line (74).

2. Extracorporeal blood treatment apparatus (1) according to the preceding claim, wherein the pressure valve (76), after switching from the interception position to the flow position, is configured to maintain the flow position as long as said differential pressure is greater than the closure pressure (P2),and wherein the pressure valve (76), when in the interception position, is configured to maintain the intercepting position up to the aperture pressure (P1 ).

3. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, wherein the pressure valve (76) is configured, by switching from the interception position to the flow position and vice versa, to generate a pulsed infusion of the infusion fluid into the blood circuit (17), wherein each pulse has - 48 -P51117PC00a duration (T) and two subsequent pulses are separated by a bolus period (Tboius), a dimensionless factor (a) being defined as:Ta = - T1boluswherein:a is the dimensionless factor;T is the pulse duration; andis a time between two subsequent pulseswherein the dimensionless factor (a) is lower than 0.7, in particular lower than 0.6 and more in detail lower than 0.5.

4. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claim 3, wherein the dimensionless factor (a) is:20 15a < 1 — — - and in particular a < 1 — — - ' bolus ' boluswherein:is a time expressed in minutes.

5. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims 3 to 4, wherein the dimensionless factor (a) is:wherein:is a time expressed in minutes.

6. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, wherein the differential pressure is defined between a valve inlet of the pressure valve (76) and a valve outlet of the pressure valve (76), wherein the valve inlet faces an upstream tract of the fluid infusion line (74) towards the second end (74b) of the fluid infusion line (74), and the valve outlet faces a downstream tract of the fluid infusion line (74) towards the first end (74a) of the fluid infusion line (74),and wherein the pressure valve (76) is configured to switch from the interception position to the flow position when a fluid pressure at the valve inlet is higher than a fluid pressure at the valve outlet by at least said differential pressure,and wherein the pressure valve (76), when arranged in the flow position, is configured to allow a fluid flow in the fluid infusion line (74) from the second end (74b) to the first end (74a) of the fluid infusion line (74),- 49 -P51117PC00and wherein the pressure valve (76), when arranged in the intercepting position, is configured to prevent, or reduce with respect to the flow position, a fluid flow in the fluid infusion line (74) from the second end (74b) to the first end (74a) of the fluid infusion line (74).

7. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, wherein the pressure valve (76) is a passive valve neither controlled nor controllable by a control unit or an electronic circuit and is configured to switch between the flow position and the interception position based on said differential pressure.

8. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, wherein a fluid passage cross section of the pressure valve (76), when the pressure valve (76) switches from the interception position to the flow position, is configured to move from:a minimal or zero fluid passage cross section (Smin) of the interception position, toa maximum fluid passage cross section (Smax) of the flow position,wherein the minimal or zero fluid passage cross section (Smin) corresponds to a minimum size of the fluid passage cross section of the pressure valve (76),wherein the maximum fluid passage cross section (Smax) corresponds to a maximum size of the fluid passage cross section of the pressure valve (76), andwherein the fluid passage cross section of the pressure valve (76) is configured to reduce from said maximum fluid passage cross section (Smax) to said minimal or zero fluid passage cross section (Smin) as the differential pressure drops from the aperture pressure (P1) to and below the closure pressure (P2).

9. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, wherein the pressure valve (76) is a duckbill valve or a cross-cut valve or a cross-slit valve, the pressure valve (76) being in one piece, and is made of a silicone or rubber or plastic material.

10. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, wherein the pressure valve (76) comprises a dome-shaped or hemispherical diaphragm at least when arranged in the interception position, said diaphragm including at least one through cut (77) configured to selectively allow and prevent fluid flow,wherein:when the pressure valve (76) is in the interception position, the at least one through cut (77) is closed to prevent or reduce fluid flow in the fluid infusion line (74),when the pressure valve (76) is in the flow position, the at least one through cut (77) is open to allow fluid flow in the fluid infusion line (74),the dome-shaped or hemispherical diaphragm deforming, in particular inverting its concavity, when switching between the flow position and the interception position.- 50 -P51117PC0011. Extracorporeal blood treatment apparatus (1) according to the preceding claim and in combination with claim 7, wherein the dome-shaped or hemispherical diaphragm defines a convex side (76a) and a concave side (76b), and wherein, when the pressure valve (76) is in the interception position, the convex side (76a) faces the upstream tract of the fluid infusion line (74) and the concave side (76b) faces the downstream side of the fluid infusion line (74),and wherein the at least one through cut (77) comprises a first through cut and a second through cut crossing each other, wherein the first through cut intersects the second through cut at a midpoint of the second through cut, and wherein the second through cut intersect the first through cut at a midpoint of the first through cut.

12. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, wherein a tract of the fluid infusion line (74) between the pressure valve (76) and a pump tract (74p) of the fluid infusion line (74) defines a compliant circuit section, the compliant circuit section comprising either or both:• a compliant tube made of a flexible elastic material such as silicone or PVC; and / or• a compliant chamber (96) located along the tract,optionally wherein the compliant circuit section has an inner volume increasing between 0.5 ml and 4 ml every 1 bar pressure increase.

13. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, wherein the fluid infusion line comprises a pump tract (74p) configured to be coupled to an infusion pump (75) of the extracorporeal blood treatment apparatus (1), said pump tract (74p) being interposed along the fluid infusion line (74) between the pressure valve (76) and the second end (74b) of the fluid infusion line (74), and being located upstream of the pressure valve (76) along an infusion direction, the pressure valve being in particular at a maximum distance from the first end (74a) of the fluid infusion line (74) less than 100 mm; wherein the upstream tract of the fluid infusion line (74) defines an inner volume, between said pressure valve (76) and the pump tract (74p), configured to house the infusion fluid,wherein said inner volume, measured in a rest condition wherein no pressure is applied inside the infusion line (74), is optionally comprised between 0.5 ml and 50 ml.

14. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, wherein: the disposable set (100) comprises a degassing chamber (80) arranged on the blood return line (7) between the first end (7a) and the second end (7b) of the blood return line (7), said degassing chamber (80) comprising:o a blood inlet (81) for blood entry;o a blood outlet (82) for blood output;o a fluid infusion inlet (83) connected to the first end (74a) of the fluid infusion line (74); or wherein- 51 -P51117PC00the first end (7a) of the fluid infusion line (74) is connected to the return line (7) in particular downstream the degassing chamber (80), wherein the blood return line (7) includes a 3-way connector comprising a blood inlet connected to an upstream tract of the blood return line (7), a blood outlet connected to a downstream tract of the blood return line (7), and an infusion inlet connected to the first end (74a) of the fluid infusion line (74), in particular wherein the connector is distinct from the degassing chamber (80).

15. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, comprising:- a pre-infusion substance source (10) comprising a regional anticoagulant such as a citrate solution; - a pre-infusion line (51) extending between a first end (51a) connected to the blood withdrawal line (6), in particular upstream a blood pump tract (6p), and a second end (51b) connected to the pre-infusion substance source (10);- the infusion substance source (11) fluidly connected to the second end (74b) of the fluid infusion line (74), wherein the infusion substance source (11) comprises a solution containing concentrated calcium, for example in a concentration between 50 mmol / L and 500 mmol / L.

16. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, wherein the pressure valve (76) is a bi-stable valve comprising a first stable position defined by the flow position, and a second stable position defined by the interception position, the aperture pressure (P1) is comprised between 0.5 bar and 10 bar and the closure pressure (P2) is comprised between 0 bar and 0.5 bar.

17. Extracorporeal blood treatment apparatus (1)wherein during the pulsed infusion, a dimensionless factor (a) is defined as:Qcaa = — —Qinfwherein:a is the dimensionless factor;Qca is the substantially constant flow rate in the fluid infusion line (74); andQinf is an average infusion flow rate of a pulse during the pulsed infusion,wherein the dimensionless factor (a) is:<>wherein:Tboius is a time expressed in minutes.P51117PC0018. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, wherein said set speed of the infusion pump (75) is configured to define a flow rate in the infusion line (74) comprised between 2 ml / h and 200 ml / h, specifically 3 ml / h to 50 ml / h.

19. Extracorporeal blood treatment apparatus (1) according to any one of the preceding claims, further comprising an air bubble sensor (55) located on the blood return line (7), the infusion line (74) being arranged to infuse the infusion fluid upstream of the air bubble sensor (55).

20. Disposable set (100) for an extracorporeal blood treatment apparatus (1), the disposable set (100) comprising:a blood circuit (17) comprising:o a blood withdrawal line (6) extending between a first end (6a) connected or connectable to a treatment unit (101) and a second end (6b) for connection to a patient,o a blood return line (7) extending between a first end (7a) connected or connectable to the treatment unit (101) and a second end (7b) for connection to the patient;a fluid infusion line (74) extending between a first end (74a) connected to the blood circuit (17) and a second end (74b) for connection to an infusion substance source (11) configured to contain an infusion fluid, a pressure valve (76) located on the fluid infusion line (74) and interposed between the first end (74a) and the second end (74b) of the fluid infusion line (74), the pressure valve (76) being movable between a flow position and an interception position, wherein the pressure valve (76) is configured to switch:o from the interception position to the flow position when a differential pressure across the pressure valve (76) exceeds an aperture pressure (P1); ando from the flow position to the interception position when said differential pressure across the pressure valve (76) falls below a closure pressure (P2);wherein the closure pressure (P2) is below the aperture pressure (P1).

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