Patent Publication Number: US-2009230058-A1

Title: Control of bubble formation in extracorporeal circulation

Description:
TECHNICAL FIELD 
     The present invention relates to control of bubble formation in a body fluid during extracorporeal circulation. More precisely, the present invention relates to minimization of the bubble formation. 
     BACKGROUND OF THE INVENTION 
     Primarily during heart operations there is a transient need to replace the function of the heart and lungs by artificial means. Also in more chronic disease states as e.g. during severe pulmonary, cardiac, or renal failure, maintenance of life can be upheld by different artificial means until an organ for transplantation becomes available. In many clinical situations there is a need for an extracorporeal circuit wherein the artificial organ is incorporated. 
     The contact of blood on surfaces made out of foreign material inevitably initiates blood coagulation and the formation of clots. This is controlled by the use of anticoagulant drugs. Also gas bubbles are easily formed in blood, which is propelled into the circulation of a living being during extracorporeal circulation. This phenomenon is due to cavitation, temperature gradients, and differences in the amount of gases dissolved between own and incoming blood. In the case of heart surgery the extracorporeal circuit contains a gas-exchange device i.e. an oxygenator, which is used not only for oxygenation but also for the disposal of carbon dioxide. The close contact between blood and gas in the oxygenator poses even higher risks for inadvertent entry of gas bubbles into the circulating blood. 
     At present, the avoidance of bubble formation during heart surgery include the change of the clinical use of bubble-oxygenators into the membrane-type, the avoidance of high temperature gradients, and a controlled use of suction in the operating field. All heart-lung machines contain an air bubble sensor that warns the perfusionist, i.e. the person maneuvering the heart-lung machine, of the appearance of small bubbles and immediately stops the main pump when larger bubbles appear. Typically, the bubble sensor can discern bubbles with a diameter of approximately 0.3 mm, but stops the main pump first when a bubble with a diameter of 3-5 mm is recognized. 
     There are numerous technical solutions in the prior art to separate already formed bubbles from circulation. In the patent document U.S. Pat. No. 5,362,406 a method is disclosed using a porous sponge material for inducing small bubbles to coalesce and the formed larger bubbles are then subsequently vented from the extracorporeal circuit. Similar in construction are the filtering devices disclosed in the patent document U.S. Pat. No. 6,328,789 B1. The patent document U.S. Pat. No. 6,478,962 discloses a method for bubble separation by strong radial acceleration forces thus concentrating bubbles to the center of the accelerated blood flow. 
     However, there is no device available intended to diminish the generation of gas bubbles i.e. the formation of gas bubbles during e.g. heart surgery. In a blood bubble, in the liquid-gas interface, there is an approximately 40-100 Å (i.e. 4-10 nanometer) deep layer of lipoproteins that denaturate due to direct contact with the foreign material, e.g. gas. In turn, the Hageman factor is activated which initiates coagulation and the concomitant adverse consumption of factors promoting coagulation, which in the post-pump period are desperately needed to prevent bleeding from the surgical wound. It seems therefore more beneficial and logical to inhibit the bubble formation in the blood during extracorporeal circulation rather than to allow bubble formation and subsequent compulsory removal of bubbles. 
     To inhibit bubble formation in a liquid, the method of lowering the partial pressures of dissolved gases in the liquid has been employed for industrial design. The US patent document 2003/0205831 A1 discloses a method for the use in vehicle glass repair. A vacuum pump coupled to the repair space degasses both the damaged area and the repair material. This method is not intended for circulating fluids and cannot be used in extra-corporeal circulation during e.g. heart surgery. 
     The method disclosed in U.S. Pat. Nos. 5,772,736; 5,645,625; 5,425,803, and EP 0 598 424 A3 is used on moving liquids and its purpose is to eliminate large overpressure of a dissolved propellant gas such as helium. An application of the degassing module as described in these patents in extracorporeal circulation would be of no avail, since the pressure of dissolved gas in the liquid is reduced only to ambient atmospheric pressure—a situation already present in the oxygenator of any heart-lung machine setup. 
     The patent document WO02/100510 A1 discloses a method to degas preferably water by applying vacuum over a gas-permeable membrane letting the liquid flow on the other side. The problem solved with this method is how to generate vacuum without great loss of water, since water is used in the high stream ejector type production of vacuum, based on Bernoulli&#39;s principle. A problem with this setup is that the returned water used for vacuum generation becomes supersaturated with the removed gas and it is supposed that time will provide equilibrium of dissolved gas in the returned water with the ambient air and thus diminish excess gas before return to the reservoir. To implement this method on blood would be hazardous, most probably due to bubble formation in the returned, initially gas-supersaturated blood but also due to the blood injury that would ensue during the vigorous pumping of blood for generation of vacuum. 
     The U.S. Pat. No. 6,596,058 discloses a method for degassing the mobile phase in high performance liquid chromatography. The method utilizes application of reduced pressure or vacuum to the solvent over a liquid-impermeable and gas-permeable membrane. This document is focused on the manufacturing, without supporting structures, of the gas-permeable membrane dividing the fluid and vacuum portions of the degassing chamber. 
     PURPOSE OF THE INVENTION 
     The purpose of the present invention is to control, and especially to minimize, bubble formation and bubble size in a body fluid during extracorporeal circulation of a living being. 
     An aspect is to control dissolved gas in the fluid in an extracorporeal circulation circuit. 
     BRIEF DESCRIPTION OF THE INVENTION 
     The purpose of the invention is fulfilled by a system, a method and apparatus according to the independent claims. Preferred embodiments of the invention are set out in the dependent claims. 
     The invention fulfills the purpose by decreasing the total gas pressure of the fresh gas distributed to a gas exchanging compartment of a gas exchange means comprised in an extracorporeal circuit. This can for example be accomplished by a combination of a) the complete airtight closure of the gas compartment of the gas exchange means except for the gas inlet(s) and outlet(s); b) connecting a fresh gas tubing to the gas inlet(s) of the gas exchange means through gastight and incollapsable tubes; c) safeguarding against an inadvertent overpressurization of the gastight constructed gas exchange means by e.g. safety valve(s); d) providing an alerting alarm device for warning the user against too high a pressure difference over the gas-exchange membrane; e) attaching through gastight and incollapsable tubes a suction apparatus to the gas outlet(s) for the control of the total gas pressure over the gas-exchange membrane in the gas exchange means, thus controlling the dissolved amount of gas of the blood leaving the gas exchange means; f) and/or connecting the gas exhaust tubing of the suction device mentioned under e) to a gas outlet so that the appropriate disposal of volatile anesthetic gases can be performed. 
     The subatmospheric pressure in the above described airtight gas exchange means will not only extract dissolved gas of the blood but also induce formed bubbles entering into the gas exchange means to increase in volume proportionally. Since there is formation of a denatured layer of lipoproteins in the gas-liquid interface of blood, the transient volume increase of a bubble passing through a gas exchange means with subatmospheric pressure may enlarge the total bubble surface area and thus the total amount of irreversibly denatured lipoprotein. This can be counteracted by the application of a proportionally increased hydrostatic blood pressure in the blood compartment of the gas exchange means. 
     Furthermore, by increasing the hydrostatic pressure of a liquid containing bubbles it is possible to force gas molecules from the gas bubble into a soluble state in the liquid. Hydrostatic pressure high enough may even annihilate the bubble completely. In one embodiment of the invention, a supplementary device for the temporary increase of hydrostatic pressure is incorporated for this purpose in the tubing of the extracorporeal circuit, preferably between the flow control means and the gas exchange means. 
    
    
     
       DESCRIPTION OF THE DRAWINGS 
       The present invention will be described in further detail below, with reference to the accompanying drawing, in which: 
         FIG. 1  schematically illustrates a first exemplifying embodiment of the invention; 
         FIG. 2  schematically illustrates a second exemplifying embodiment of the invention; and 
         FIG. 3  schematically illustrates a third exemplifying embodiment of the invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention relates to a system, an apparatus, and a method for controlling the bubble formation in an extracorporeal circulatory procedure. It is intended for heart surgery, but can also be employed in a multitude of clinical applications, e.g. dialysis, in which it is desirable to extracorporeally circulate a body fluid. Thus the oxygenator can be modified according to different clinical prerequisites and the flow can also be generated by the arterial-venous pressure difference rather than a pump. 
     Exemplifying embodiments of the present invention will be described in more detail with reference to  FIGS. 1-3 , in which the same reference numerals are used for the same or similar components or features. 
       FIG. 1  schematically depicts a first embodiment of a system according to the present invention, which system  10  can be used in e.g. open heart surgery. The figure shows how the application of vacuum to a gas exchange means, such as an oxygenator, can be employed and also how an increased hydrostatic blood pressure during blood passage through the oxygenator can be generated according to the invention and setup of the device during extracorporeal perfusion. 
     An embodiment of the inventive system  10 , according to  FIG. 1 , comprises tubings  111   a  by means of which venous blood can be diverted from a patient  110  to an extracorporeal venous reservoir  112 . In this description, the tubing  111   a  will also be referred to as a venous line  111   a . However it should be understood that the tubing also can be an arterial line in applications where arterial blood is to be withdrawn from the patient. The venous reservoir  112  is configured to collect, by gravity force or by an applied subatmospheric pressure, the venous blood from the patient. Also blood sucked from an operating field can be reused by repumping it into the reservoir  112 . Large gas bubbles in blood that enter the venous reservoir  112  will rise by gravitation to the surface and are thus disposed of, since the reservoir is open to ambient air or an applied subatmospheric pressure. 
     The system can further comprise a flow control means  113  arranged to generate propellant energy to the blood withdrawn from the patient  110 , whereby the withdrawn blood is circulated in an extracorporeal circuit. The flow control means  113  can for example be a pumping means realized as a main pump  113  of a heart-lung machine (not shown). As illustrated in  FIG. 1 , the flow control means  113  is arranged at tubings  111   b  between the reservoir  112  and a gas exchange means  114 . In the present description text and in order to exemplify the invention, reference will be made to an oxygenator  114 . However, it should be understood that the gas exchange means can be realized as another kind of device capable of diminishing and/or exchanging gas comprised in a fluid. 
     The oxygenator  114  is connected or connectable to the extracorporeal circuit and as shown in the figures, the oxygenator  114  is in the shown embodiment arranged downstream the reservoir  112  and the flow control means  113 . The oxygenator  114  is configured to provide gas exchange of the withdrawn blood circulated in the extracorporeal circuit. The extracorporeal circuit comprises further tubings  115  by means of which oxygenated blood flows from the oxygenator  114  back to the patient  110 . In the embodiment shown in  FIG. 1 , wherein venous blood is withdrawn, the blood flows back to the patient  110  via an arterial line  115  and an arterial cannula  116  inserted into an artery of the patient  110 , however it should be understood that the tubing also can be a venous line in applications where arterial or venous blood is to be withdrawn from the patient. 
     The oxygenator  114  comprises a first compartment  117  also called the blood compartment  117  when blood is the fluid flowing in the circuit. The oxygenator  114  comprises further a gas-fluid separating membrane or a gas-blood separating membrane  118  through which the gas exchange and exhaust occurs, and a second compartment  119  also called the gas compartment  119 . 
     The system comprises also a gas source  120  by means of which fresh gas is supplied to the oxygenator  114  via a gas supply tube  121  and a gas inlet  122  of the second compartment  119  of the oxygenator  114 . The fresh gas can for example be a mixture of oxygen, nitrogen, and a volatile anesthetic agent and is supplied after pressure reduction via a gas flow-meter from the gas source  120 . The membrane  118  is configured permeable to the supplied fresh gas, whereby gas exchange between fresh gas and venous blood occurs since the partial pressures of gases in the gas compartment  119  and the partial pressures of gases dissolved in blood passing through the blood compartment  117  tend to equalize. After having passed the gas compartment  119  of the oxygenator  114 , the gas flow is directed to a gas outlet  123  of the oxygenator  114 . 
     According to the present invention, the gas flows via a gas outlet tubing  124  connected to the gas outlet  123  to an antibubble control unit  125 . The gas is subsequently exhausted via an exhaust tube  126  of the antibubble control unit  125  into ambient air or into an exhaust system of the facility. The tubing  124  is preferably made of material that is uncollapsable and airtight. The antibubble control unit comprises a suction device  160  configured to generate a low gas pressure which is propagated via the tube  124  into the gas department  119  of the oxygenator  114 . It also comprises a central computer  161  for controlling the performance of the different parts of the system, e.g. the set subatmospheric pressure at a setting device  135  of the gas compartment  119  of the oxygenator  114 , the increase in hydrostatic pressure in the blood compartment  117  of the oxygenator  114  or elsewhere, and it may also display parameters of interest on display means  136 ,  137 , and  138  such as pressures, fresh gas oxygen concentration and embolic load. 
     The oxygenator  114  is further open to ambient air through an opening  127  situated close to the gas outlet  123 . This is to prevent a supraatmospheric pressure to develop in the gas compartment  119  in case the gas outlet  123  or gas outlet tubing  124  is unintentionally obstructed. An overpressure in the gas compartment  119  could lead to disastrous air leakage into the blood flow of the arterial line, since the membrane  118  is not always airtight but in most clinical applications composed of a micro-porous material that easily may pass gaseous emboli through the membrane into the liquid, e.g. blood, but does not, due to capillary forces, pass the liquid over the membrane into the gas. 
     According to embodiments of the present invention, the bubble formation in the blood is to be diminished by lowering the amount of dissolved gases in the blood. This is accomplished by decreasing the gas pressure in the gas compartment  119  of the oxygenator  114 . For this purpose a suction apparatus  160  is integrated in the antibubble control unit  125 . The suction apparatus  160  can be realized as an ordinary, high-quality suction device that is capable of generating subatmospheric pressures of approximately 0.1 bar. In embodiments of the invention, the suction apparatus  160  is integrated into the antibubble control unit  125 , which, in such an embodiment, also contains means to perform the method of the present invention in a safe manner. 
     The method of the present invention implies that a preset level of vacuum can be maintained in the gas compartment  119  of the oxygenator  114 . In order to achieve this, it is desirable that the oxygenator  114  is constructed gas-tight, which means that an anti-overpressurization safety opening  127  must be closed during the vacuum-operation. This safety measure can be accomplished e.g. with a spring type, one-way, valve  128  arranged at the safety opening  127 . The valve  128  opens in case of an overpressure and closes in case of a pressure lower than the ambient atmospheric pressure in the gas compartment  119 . 
     The present invention decreases dissolved or comprised gases in the blood. Nitrogen, oxygen, and carbon dioxide and water vapour constitute more than about 99% of these gases under normal circumstances. The organism needs a minimum level of partial pressure of oxygen to sustain aerobic metabolism. Dry air is constituted by approximately 78% nitrogen and 21% oxygen, and the nitrogen is not needed for metabolism. If nitrogen is substituted for oxygen, one can decrease the total gas pressure to 1/5 and still have the same partial pressure of oxygen available for the organism. When vacuum is applied according to the invention, the oxygenator  114  has to be constructed airtight, as mentioned above. Also all connections and tubing  121  of the fresh gas source  120  have to be airtight as depicted in  FIG. 1  by the hatched area. The gas outlet tubing  124  is also constructed airtight as needed for any suction apparatus to function. 
     Today, during conventional extracorporeal circulation in heart surgery, in case there is an air leak in the fresh gas tubing it would perhaps not be noted since the direction of leakage of fresh gas would be out of the oxygenator into the ambient air. However, in case of leakage during vacuum operation there would be an entrance of ambient air (consisting of 78% nitrogen) into the oxygenator, changing the effective level of oxygen in the fresh gas to a lower level. Therefore, the perfusionist has to check for leaks during the procedure and has to monitor the partial pressure of oxygen preferably at the site of gas outlet. 
     Therefore, in the present invention, an oxygen sensor  129  can be arranged at the gas outlet tubing  124  and configured to monitor the partial pressure of oxygen in the gas leaving the oxygenator  114  via the gas outlet  123 . The signal from the oxygen sensor  129  can be diverted to, processed in and presented to a perfusionist by means of the antibubble control unit  125 . 
     According to the invention, the already formed bubbles entering into the oxygenator during the vacuum operation will change in volume proportionally to the decreased total gas pressures exerted on the blood. During the passage through the oxygenator when vacuum is applied, a bubble will thus increase in size. There is formation of a denatured layer of lipoproteins in the gas-blood interface and the transient volume increase of a bubble passing an oxygenator may irreversibly enlarge the total bubble surface of denatured lipoprotein. For example, if bubble volume is increased by 50%, the surface area will increase by approximately 31% (100×(1.5 1/3 ) 2 −100). Even after the disappearance of gas inside a blood bubble the irreversibly denatured surface layer of lipoproteins persists and may form an embolus capable of obstructing capillaries and perhaps also induce a reaction of the body as if it were a foreign body. It may therefore be beneficial to counteract this effect on bubble size due to vacuum application. To this end the present invention may also include the step of increasing transiently the hydrostatic blood pressure in the blood during the passage of the blood compartment of the oxygenator. In clinical practice, though, this may not be deemed necessary. 
     During clinical perfusion of today, the hydrostatic pressures in the blood tubing before and after the oxygenator  114  is measured by means of pressure sensors  130  and  131 , respectively. The pressure measurement is done in order to monitor the pressure gradient generated by the oxygenator  114  and thus to early detect e.g. oxygenator malfunction. In the present invention, the signals from these pressure sensors  130 ,  131  are fed directly or via a heart-lung machine (not shown) into the antibubble control unit  125 . The mean and maximum/minimum pressures in the blood compartment  117  of the oxygenator  114  may be, together with the pressure signal of measured vacuum  139  of the gas compartment  119 , used for feedback calculation of appropriate increased hydrostatic pressure that should be applied in the blood compartment  117  of the oxygenator  114  to counteract the chosen level of subatmospheric pressure in the gas compartment  119  of the oxygenator  114  in order to maintain bubble size. Such calculations are performed in a central computer  161  comprised in the antibubble control unit  125 . 
     The blood pressure in the blood compartment  117  of the oxygenator  114  may be measured directly from a location in the compartment  117 , or deduced from measurements from other locations  130 ,  131 . The pressure in the blood compartment  117  of the oxygenator  114  can be manipulated or controlled by a clamping device  132  which in turn can be controlled by the antibubble control unit  125 . The clamping device  132  is constructed to be able to adjust to very small mechanical changes and to have a small time-constant and hysteresis. The clamping device  132  is preferably easily detachable from the arterial line  115 , in case of e.g. malfunction. 
     A second embodiment of the invention comprises means for the temporary increase of hydrostatic pressure of the blood in the extracorporeal circuit. The purpose of this pressure increasing means is to reduce bubble volume of gas by application of an increased hydrostatic pressure to the bubble-carrying liquid/blood. The increased hydrostatic pressure of blood will be propagated into the gas bubble, thus forcing gas from the bubble into solution, i.e. from gas phase to liquid phase. Subsequently, a new steady state is reached rendering the bubbles smaller not only because of the higher hydrostatic pressure but also from the loss of a portion of the original contained gas of the bubbles that becomes dissolved in the blood. At high enough levels of hydrostatic pressure applied and long enough time period of its application, even a complete annihilation of bubbles may be achieved. 
       FIG. 2  shows schematically the second embodiment of the invention comprising means for the temporary increase of hydrostatic pressure of the blood in the extracorporeal circuit. In this embodiment, a device for forcing gas contained in bubbles into solution by applying a temporary high hydrostatic pressure to the blood/liquid stream is incorporated. Also, in this embodiment, the pressure increasing means is realized as a high-pressure resistant reservoir  140  for circulating blood. The high-pressure resistant reservoir  140  is preferably arranged between the flow control means  113  and the oxygenator  114 . The dimension, e.g. the length, of the tubing between the reservoir  140  and the oxygenator  114  should preferably be minimized in order to allow for a minimum of time period after the pressurization in the high-pressure resistant reservoir  140  before the blood enters the gas-exchanging part  119  of the oxygenator  114 . Otherwise, in time, bubbles may regain their former size due to the movement of gas from the supersaturated liquid, just having left the high-pressure resistant reservoir  140 , back into existing bubbles, or forming new ones. In this instance it is also important that the outlet  141  from the high-pressure resistant reservoir  140  into ambient atmospheric pressure is hydrodynamically shaped in order to minimize bubble formation due to turbulent flow. 
     The volume of the high-pressure resistant reservoir  140  is preferably chosen so that enough time is allowed for the redistribution of gas from bubbles into a dissolved state, but also taking into consideration the benefits of minimal priming volumes of the extra-corporeal circuitry. If, for example, a blood flow of 4.5/min and a time period of 10 seconds of high pressurization are needed, then the volume of the high-pressure resistant reservoir  140  should be approximately 0.75 liters. The volume of the reservoir  140  may be reduced when higher pressure is utilized, keeping blood flow constant. 
     The hydrostatic pressure in the high-pressure resistant reservoir  140  can be manipulated by a clamping device  142  controlled by the antibubble control unit  125  and configured to regulate the outflow resistance from the high-pressure resistant reservoir  140 . The clamping device  142  is further constructed to be able to adjust to very small mechanical changes and to have a small time-constant and hysteresis. Also, it has to be easily detachable from the arterial line, in case of malfunction. In this embodiment of the invention, a pressure sensor  143  is arranged at the high-pressure resistant reservoir  140 . The pressure sensor  143  is configured to register the pressure in the reservoir  140  and transmit a registered pressure value as a pressure signal to the antibubble control unit  125 . In the central computer  161  of the antibubble control unit  125 , the pressure value is compared to a set value  144  chosen by the perfusionist. Further, the central computer  161  generates an appropriate control signal by means of which signal the operation of the clamping device  142  is controlled, whereby a desired pressure level can be achieved in the high-pressure resistant reservoir  140 . The signal from the pressure monitor  143  is preferably presented to the perfusionist on the antibubble control unit  125  display. 
     The antibubble control unit  125  in the present invention contains the function to generate subatmospheric pressures by a suction device  160  contained in the antibubble control unit  125  and to generate increased hydrostatic pressure in the blood compartment  117  of the oxygenator  114 . The central computer  161  of the antibubble control unit  125  can also be configured to calculate transmembrane pressure over the oxygenator membrane  118 , and to alert an alarm signal by means of a sound alarm  133  and/or by means of a visible alarm  134  when reaching non-allowable limits. 
     The antibubble control unit  125  can be configured to comprise a setting device  135  by means of which a perfusionist is able to enter a chosen level of subatmospheric pressure desired in the gas compartment  119 . The antibubble control unit  125  can further comprise a computer  161  configured to calculate, based on the preset level of vacuum, an appropriate level of increased pressure in the blood compartment  117  in order to avoid enlargement of preformed bubbles entering the oxygenator  114 . The pressure signals registered by the pressure sensors  130 ,  131  over the blood compartment  117  can be used for electronic feedback control of the adjustment of the clamp  132  to generate an appropriate increased level of pressure in the blood compartment  117 . The antibubble control unit  125  can also contain one or more displays  136 ,  137 , and  138  for presenting for example actual measured levels of gas compartment pressure  139 , blood compartment pressure  130 ,  131  and gas flow oxygen concentration  129 , respectively. These presented parameters or, when appropriate, their calculated differences can all be connected into one or several common or separate alarm devices  133 ,  134 . 
     In the second embodiment of the invention, the antibubble control unit  125  further comprises means configured to feed-back regulate the pressure in a high-pressure resistant reservoir  140 . The feed-back means can comprise setting means  144  for setting the pressure level in the high-pressure resistant reservoir  140  and display means  145  to monitor the generation of the pressure in the high-pressure resistant reservoir  140 . 
     It is important to be able to measure changes in bubble formation when the methods and equipment according to this invention are employed. In a third embodiment of the invention, the inventive system contains means to monitor and document the occurrence of bubbles more properly than currently employed. Heart-lung machines contain bubble monitoring devices with sensors to be attached to the tubing and which are configured to warn the perfusionist when bubbles appear and they may also be configured to automa-tically halt the main pump in case larger bubbles occur. The sensitivity of the bubble sensors of heart-lung machines in common use, e.g. in Jostra HLM 20 and Stockert S3, is 300 micrometers, which is to be compared with the size of blood capillaries which may be in the range of the diameter of a single red blood cell i.e. 7 micrometers. The bubble detecting device already equipped into a heart-lung machine may therefore be too insensitive. 
       FIG. 3  shows schematically a third embodiment of the present invention. In this embodiment one or several bubble sensors for quality control are attached directly to the arterial line  115  and/or to a tube containing filtered plasma from the blood of the arterial line. As illustrated in  FIG. 3 , a high sensitivity first bubble sensor  146  is attached to the arterial line  115  and communicatively connected to the antibubble control unit  125 . The high sensitivity bubble sensor  146  could for example be realized as a bubble detector with sensitivity down to sizes when the corpuscular elements of the blood come into play i.e. about 10-15 micrometers. The signal from the bubble sensor is handled by the central computer  161  of the antibubble control unit  125  which may show the occurrence of gas emboli in a display means, sound or light an alarm, or even halt the pump. 
     Sensors of higher sensitivity than mentioned above may be functional only with filtered blood i.e. blood plasma, where no formed elements of blood such as red or white blood cells or platelets appear. Thus in order to be able to use such sensors, it may be necessary to incorporate a blood filtering device  147  from which blood plasma is bypassed and sensed for emboli by a second bubble sensor  148  having a higher accuracy, discerning bubbles down to fractions of a micrometer. 
     The size and frequency of occurrence of the bubbles may be presented to the perfusionist visually on display means  137 ,  138  and/or audibly by means of audible means  133  and on a display of the antibubble control unit  125 , forcing the perfusionist to take appropriate action. 
     The present invention also relates to a kit containing disposable articles comprises one or several pressure measurement tubes according to the specifications above, configured to be attached to the measurement outlets of the blood tubing and oxygenator, respectively. The kit can further comprise a gas-tight oxygenator and optionally a high-pressure resistant reservoir. 
     The present invention has been described in detail above but it is obvious to a person skilled in the art that the invention may be modified in other ways within the scope of the appended claims.