Patent Publication Number: US-2006009728-A1

Title: Extracorporeal blood handling system with automatic flow control and methods of use

Description:
FIELD OF THE INVENTION  
      The present invention relates to an extracorporeal blood handling system with automatic flow control and methods for use for monitoring and detecting error conditions, and modulating flow through the extracorporeal blood handling system in response to the detected error conditions.  
     BACKGROUND OF THE INVENTION  
      For more than thirty years, vascular diseases have been treated using open surgical procedures. In 1999 alone, 753,000 open-heart procedures, including coronary artery bypass grafting (CABG), valve replacements, and heart transplants, were performed. During a typical CABG procedure, a sternotomy is performed to gain access to the pericardial sac, the patient is put on cardiopulmonary bypass (CPB), and the heart is stopped using a cardioplegia solution.  
      Generally, previously-known CPB is accomplished by constructing an extracorporeal blood handling system including, inter alia, a venous line, a venous reservoir, a centrifugal or roller pump that perfuses blood through the extracorporeal circuit and the patient, an oxygenator for oxygenating the blood, an arterial line for returning oxygenated blood to the patient, and an arterial filter located in the arterial line. The pump in previously known methods of CPB is placed after the venous reservoir and the venous flow into the reservoir is driven by negative pressure in this line from a siphon and not the pump. In order to minimize the diameter and cannula size required for the venous line, vacuum is often applied to the reservoir, as described, for example, in U.S. Pat. No. 6,017,493 to Cambron. The use of a venous reservoir provides compliance in the blood treatment system so the venous flow may be controlled independently of the arterial or return flow to the patient.  
      Previously-known methods of CPB are susceptible to several error or trigger conditions. For instance, one trigger condition is the inadvertent introduction of air into the extracorporeal circuit. This may occur in a number of ways, including inadvertent opening of a vent line, improper priming of the circuit, or by turning the heart during surgery. In addition, differences between blood inflow to a venous reservoir and outflow from the venous reservoir due to the pump head can lead to depletion of the reservoir and the entrainment of large amounts of air. If returned to the patient, air can cause significant patient injury such as brain damage, cardiac dysfunction, and myocardial damage. Further, an air-blood mixture may cause turbulence and high shear stresses within the circuit, resulting in hemolysis and humoral and/or cellular activation.  
      Previously known CPB systems, such as the S3 System sold by Stockert GmbH, Munich, Germany, the HL 20 Heart Lung Machine sold by Jostra Corp., The Woodlands, Tex., USA and the Sarns Modular Perfusion System 8000, sold by Terumo Cardiovascular Systems, Ann Arbor, Mich., USA, each include a level detector in the venous reservoir that slows and then stops delivery of blood to a patient if the volume of blood in the venous reservoir falls below a minimum volume. Each of these systems also includes a bubble detector that abruptly stops the pump if a predetermined number of bubbles larger than a predetermined size are detected.  
      The system shutdown strategy used in previously known CPB systems is designed to prevent de-priming of the venous reservoir and other components of the CPB circuit until the perfusionist can correct the problem. Due to the extended periods of time required to prime previously-known CPB systems, such a strategy is critical to avoid de-priming. Unfortunately, this strategy leads to no forward flow to the patient, with potentially serious consequences if flow is not restored promptly.  
      Another previously-known method for handling air entrained in the blood is described in U.S. Pat. No. 5,188,604 to Orth. The system described in that patent includes an air sensor disposed in the arterial line, a controller, and a series of solenoid-controlled valves, and a shunt circuit. If air is detected in blood passing to the arterial line, the controller actuates the solenoid-controlled valves to stop flow in the arterial line and simultaneously opens the shunt circuit to redirect the air-laden blood back into the blood treatment system. Like the previously-described CPB systems described above, the system described in the Orth patent results in no forward flow to the patient until the error condition is corrected.  
      Another trigger condition is low venous pressure, which may be caused by occlusions within the circuit. Low venous pressure is a known risk factor for air entrainment and may result in depletion of the venous reservoir as previously discussed, thus requiring blood delivery to the patient to be suspended while the condition is corrected or the CPB system is re-primed.  
      In addition, substantial occlusion of the venous line in previously-known CPB systems may provide minimal to no reaction time for the perfusionist to correct trigger conditions. For instance, should the venous return flow stop due to a trigger condition, such as detection of a large bubble, the perfusionist has only a few seconds to stop the heart-lung machine before the bubble is pumped into the patient.  
      Yet another problem with previously-known extracorporeal blood handling systems is the substantial suction force required for proper air evacuation due to an open air source. An open air source enables the pump to pull in large amounts of air, overwhelming the ability of an air evacuation line, if present, to remove the air.  
      In view of the aforementioned limitations, it would be desirable to provide an extracorporeal blood handling system that monitors and automatically modulates blood flow in response to trigger conditions thereby increasing the time available to the perfusionist to correct trigger conditions.  
      It also would be desirable to provide an extracorporeal blood handling system that monitors and automatically modulates system operation in response to the detection of gas in the system, to enhance the ability of an air evacuation line to remove the air and avoid de-priming the pump.  
      It further would be desirable to provide an extracorporeal blood handling system that automatically modulates pump speed in response to the detection of a massive air bolus in the extracorporeal blood circuit.  
      It still further would be desirable to provide an extracorporeal blood handling system that automatically modulates system operation in response to the detection of discrete trigger conditions, monitors such conditions, and resumes normal operation when the triggering conditions resolve.  
      It even further would be desirable to provide an extracorporeal blood handling system that automatically modulates pump speed in response to the detection of low venous pressures in the extracorporeal blood circuit.  
     SUMMARY OF THE INVENTION  
      In view of the foregoing, it is an object of the present invention to provide an extracorporeal blood handling system that monitors and automatically modulates system operation in response to trigger conditions, thereby increasing the time available for an operator, e.g., the perfusionist, to correct trigger conditions.  
      It is another object of the present invention to provide an extracorporeal blood handling system that monitors and automatically modulates pump speed in response to the detection of gas in the system, to enhance the ability of an air evacuation line to remove the air and avoid depriming of the pump.  
      It is an additional object of the present invention to provide an extracorporeal blood handling system that automatically modulates system operation in response to the detection of a massive bolus of air in the circuit.  
      It is a further object of the present invention to provide an extracorporeal blood handling system that automatically modulates system operation in response to the detection of discrete triggering conditions, such a small amounts of air, monitors such conditions, and resumes normal operation once the triggering conditions subside and/or are acknowledged by the perfusionist.  
      It is an even further object of the present invention to provide an extracorporeal blood handling system that automatically modulates pump speed in response to the detection of low venous pressures.  
      These and other objects of the present invention are accomplished by providing an extracorporeal blood handling system with automatic flow control, such as a microprocessor controlled system whereby pump speed is regulated in response to detected trigger conditions.  
      In a preferred embodiment, the automatic flow control feature of the apparatus is a microprocessor-controlled system that monitors the extracorporeal circuit and automatically modulates pump speed or the system configuration in response to detected trigger conditions. The apparatus comprises an extracorporeal circuit, a controller coupled to an air evacuation system and sensors positioned to sense air and venous pressures within the extracorporeal circuit. The controller is electrically coupled to a pump, such as a centrifugal pump, to modulate the pump speed in response to detected trigger conditions in the extracorporeal circuit.  
      In a first mode, the automatic flow control system of the present invention comprises a controller coupled to at least one sensor disposed to sense air. Upon sensing a bolus of air, the microprocessor reduces the pump speed to a predetermined lower limit. The predetermined lower limit preferably is determined such that forward blood flow is maintained through the extracorporeal circuit to the patient.  
      In a second mode, the speed of the centrifugal pump is reduced in response to the detection of discrete amounts of air. In this case, the pump speed is reduced by a predetermined percentage until either the trigger condition is resolved or the pump speed reaches a predetermined lower limit.  
      In a third mode, the controller is coupled to a second sensor disposed to sense bubbles in the venous line. The speed of the centrifugal pump is reduced in response to the detection of bubbles greater than a predetermined concentration. In this case, the pump speed is reduced by a predetermined percentage until either the trigger condition is resolved or the pump speed reaches a predetermined lower limit.  
      In a fourth mode, the controller is coupled to a third sensor disposed to sense venous pressure. The speed of the centrifugal pump is reduced in response to the sensing of venous pressure below a predetermined level. In this case, the pump speed is reduced by a fixed step until the venous pressure is no longer below the predetermined level or until a predetermined lower limit is attained.  
      In alternative embodiments, the system configuration may be altered in response to the detection of trigger conditions, by constricting outflow from the system or by rerouting flowpaths within the system. In accordance with the principles of the present invention, some degree of forward flow to the patient is maintained in these alternative embodiments.  
      Methods of operating the automatic flow control features of the present invention also are provided. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      The above and other objects and advantages of the present invention will be apparent upon consideration of the following detailed description, taken in conjunction with the accompanying drawings, in which like reference characters refer to like parts throughout, and in which:  
       FIG. 1  is a schematic view of a preferred extracorporeal circuit incorporating the automatic flow control system of the present invention;  
       FIGS. 2A and 2B  are, respectively, perspective and exploded views of a preferred blood processing component suitable for implementing the automatic flow control features of the present invention;  
       FIG. 3  is a side-sectional view of the blood processing component of  FIGS. 2 and 3 ;  
       FIGS. 4A and 4B  are, respectively, perspective and cross-sectional views of a filter element of the blood processing component of  FIG. 3 ;  
       FIG. 5  is a perspective view of a preferred blood handling system incorporating the automatic flow control system of the present invention;  
       FIGS. 6A and 6B  are, respectively, representative screens depicting the display of parameters monitored and/or controlled by the blood processing system of  FIG. 5 ;  
       FIG. 7  is a flowchart depicting a first operational mode of the automatic flow control feature of the present invention for handling introduction of a massive bolus of air;  
       FIG. 8  is a flowchart depicting a first operational mode of the automatic flow control feature of the present invention for handling introduction of discrete, relatively small boluses of air;  
       FIG. 9  is a flowchart depicting a third operational mode of the automatic flow control feature of the present invention for handling the occurrence of bubbles in the venous line;  
       FIG. 10  is a flowchart depicting a fourth operational mode of the automatic flow control feature of the present invention for handling low venous pressure;  
       FIG. 11A  is a representative screen depicting the display of parameters monitored and/or controlled by the automatic flow control feature of the present invention;  
       FIG. 11B  is a representation depicting the various states of the automatic flow control button of the present invention;  
       FIG. 12A  is a graph showing how the automatic flow control system responds to the detection of low venous pressure trigger over time;  
       FIG. 12B  is a graph showing how the automatic flow control system responds to the detection of gas over time;  
       FIG. 13  is a schematic view of an alternative embodiment of an extracorporeal circuit incorporating an automatic flow control system constructed in accordance with the principles of the present invention; and  
       FIG. 14  is a schematic view of another alternative embodiment of an extracorporeal circuit incorporating the automatic flow control system constructed in accordance with the principles of the present invention. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION  
      Overview of a Preferred Blood Handling System  
      Referring to  FIG. 1 , a preferred extracorporeal blood handling system  10  suitable for use with the automatic flow control system of the present invention is described. Extracorporeal blood handling system  10  is designed to maintain a patient on full or partial bypass support, for example, during a coronary artery bypass graft procedure, in either a full-bypass or beating heart (partial bypass) mode of operation, or open heart repair procedure, typically with full-bypass mode of operation.  
      Extracorporeal blood handling system  10  includes an extracorporeal blood circuit  11  having a perfusion circuit comprising venous line  12 , perfusion line segments  13   a ,  13   b  and arterial line  14 , and a priming/reservoir circuit comprising line  16 , priming line  17 , and segments  18   a  and  18   b . The ends of perfusion line segments  13   a  (venous),  13   b  (arterial) are shown extending into the sterile field as they would appear during use, where they are coupled to venous and arterial cannulae placed in the patient, respectively.  
      Extracorporeal blood circuit  11  illustratively includes pinch clamps  19  and sampling access ports  20  disposed on various of the lines. Quick-disconnect couplings  21  are provided at the junctions of venous line  12  and venous segment of perfusion line  13   a  and arterial line  14  and arterial segment of perfusion line  13   b . These couplings  21  permit venous line  12  to be directly coupled to arterial line  14  during priming. In addition, another quick-disconnect coupling  22  is provided in line  16  to permit, for example, the inclusion of a heat exchanger when the priming circuit is used for recirculation.  
      Extracorporeal blood handling system  10  further includes an integrated blood processing component  31  coupled to a drive unit  32  and controller  33 . In addition, the blood handling system  10  includes a gas removal system including sensors  25 - 27 , and valve  36  coupled to suction source  34  via line  35 . The sensors  25 - 27 , valve  36  and drive unit  32  preferably are electrically coupled to controller  33  so that controller  33  regulates operation of valve  36  and drive unit  32  in response to output of the sensors  25 - 27 . As explained in greater detail hereinafter, the gas removal system of the present invention removes air and other gases from extracorporeal blood circuit  11  and blood processing component  31  during priming and operation of the bypass system.  
      Referring now to  FIGS. 2A, 2B  and  3 , integrated blood processing component  31  provides in a single disposable unit a blood oxygenator, blood pump, and blood filter, and optionally, a heat exchanger and/or arterial filter. Blood processing component  31  includes housing  40  having blood inlet  41 , blood outlet  42 , recirculation/cardioplegia outlet  43 , gas inlet port  44 , gas outlet port  45  and gas removal port  46 . Blood outlet  42  and recirculation outlet  43  are disposed from blood outlet manifold  47 , which is located diametrically opposite blood inlet manifold  48  on housing  40 . Blood processing component  31  preferably includes tabs  49  or other means for coupling blood processing component  31  to reusable drive unit  32 .  
      Referring to  FIG. 3 , housing  40  comprises a series of compartments, including: gas collection plenum  50 , central void  51 , upper gas plenum  52 , annular fiber bundle compartment  53 , lower gas plenum  54  and pump space  55 . In a preferred embodiment, central void  51  includes a larger diameter upper portion and a smaller diameter lower portion that couples to pump space  55 .  
      Gas collection plenum  50  encloses filter  56  that disposed within upper portion of central void  51 . Filter  56  comprises generally conical, fluid impermeable upper wall  57  having outlet  80 , baffled support structure  58  and filter material  59 . Filter  56  causes gas entrained in blood introduced into the gas collection plenum to separate and collect in the upper portions of gas collection plenum  50 . Blood inlet  41  is displaced tangentially relative to the centerline of housing  40 , so that blood passing through blood inlet  41  into gas collection plenum  50  swirls around upper wall  57 .  
      Upper wall  57  also preferably has a portion defining an interior chamber that communicates with the upper portion of gas collection plenum  50  through outlet  80 . This configuration allows any gas that passes through filter material  59  to escape through outlet  80  in upper wall  57  and be evacuated from gas collection plenum  50 . Advantageously, this feature facilitates rapid and easy priming of the blood processing component  31 .  
      Filter material  59  comprises one or multiple layers of a screen-like material, and is mounted to baffled support structure  58 . Filter material  59  serves to exclude bubbles from the blood flow by maintaining the swirling action of the blood in the central void for a sufficient time to allow the bubbles to rise to the gas collection plenum. Because the blood circulates around the outside of gas removal/blood filter  56  in central void  51 , bubbles impinge against filter material  59  tangentially, and thus “bounce off.” Filter material  59  preferably also forms a first stage of a progressive blood filter that is distributed throughout the blood processing component, and filters out relatively large particulate matter.  
      As illustrated in  FIGS. 4A and 4B , support structure  58  forms a fluid impermeable cruciform structure  63  having longitudinal struts  61  and support rings  62 . Struts  61  serve as baffles to reduce swirling of blood once the blood has passed through filter material  59 .  
      Referring again to  FIG. 3 , blood oxygenation element  70  is disposed within annular fiber bundle compartment  53 , and comprises a multiplicity of gas permeable fibers arranged in an annular bundle. As is well known in the art, the gas permeable fibers are potted near the upper and lower ends of the bundle so gas may pass through the interior of the fibers, while allowing blood to pass along the exterior of the fibers. The bundle of fibers has an upper potting region  71  that separates the blood flow region within the annular bundle from upper gas plenum  52 , and lower potting region  72  that separates blood flow region from the lower gas plenum  54 .  
      Blood passing into annular fiber bundle compartment  53  from blood inlet manifold  48  therefore flows through blood oxygenation element  70  and to blood outlet manifold  47 . The annular fiber bundle also provides some filtration and de-airing of blood passing through blood processing component  31 , by filtering out particulate matter that has passed through filter material  59  employed in gas removal/blood filter  56 . Air removal may be facilitated by the microporous structure of the fibers.  
      The lower portion of central void  51  communicates with pump space  55 , in which pump  55   a  is disposed. In a preferred embodiment, pump  55   a  is a centrifugal pump including an impeller  75  having a plurality of vanes  76  and is mounted on shaft  77  via bearings  78 . Impeller  75  preferably comprises an injection-molded part that encloses a ferromagnetic disk, so that the disk may be magnetically coupled to drive unit  32  (see  FIG. 1 ). Blood accelerated by impeller  75  is ejected from pump space  55  via a passageway that includes curved ramp  79 . Ramp  79  serves to redirect radially outward blood flow from impeller to a longitudinal flow within blood inlet manifold  48 .  
      In a preferred embodiment, oxygen is introduced into upper gas plenum  52  through gas inlet port  44  and passes through the interiors of the multiplicity of hollow fibers in blood oxygenation element  70 . Carbon dioxide, any residual oxygen, and any other gases exchanged through blood oxygenation element  70  exits into lower gas plenum  54  and are exhausted through gas outlet port  45 .  
      Referring again to  FIG. 1 , and in accordance with the present invention, the extracorporeal blood handling system  10  also includes sensors  25 ,  26  and  27  that monitor system parameters. Sensor  25  monitors the level of gas or blood in gas collection plenum  50 . Sensor  26  detects the presence of gas in venous line  12 , while sensor  27  monitors the pressure in the venous line.  
      Sensor  25  is configured to sense a parameter indicative of a level or volume of air or other gas, or detect the absence of blood, and preferably operates by a non-contact method. Suitable sensor methods include electrical-charge based, optical and acoustic methods. A resistive contact method also could be employed, in which a low electrical current is passed between adjacent electrodes only in the presence of blood.  
      Sensor  25  preferably is of a known capacitance type that detects a change in electrical capacitance between the bulk of a liquid (in this case, blood or saline) and gas. Alternatively, sensor  25  may be optical in nature, and uses a light source that has a wavelength that is minimally attenuated by blood. In this case, the light source is directed, at an oblique angle, through the blood towards a photodetector, and sensor  25  is positioned to detect the change in the refractive index of the blood (or saline prime) caused by the presence of air or other gases. In another alternative embodiment, sensors  25  may use an ultrasonic energy source and receiver to detect the presence of gas or absence of blood by the change in acoustic transmission characteristics.  
      The output of sensor  25  is supplied to controller  33  (see  FIG. 1 ), which in turn regulates valve  36 . When sensor  25  outputs a signal indicating that gas is present in the extracorporeal blood handling system  10 , controller  33  opens valve  36 , thereby coupling gas collection plenum  50  to suction source  34 . Suction source  34  may be any suitable suction source such as a vacuum bottle, pump or standard operating room suction port. Once the gas is evacuated, and sensor  25  detects blood at an appropriate level, and changes its output so that controller  33  closes valve  36 . In this manner, gas is continuously monitored and then automatically removed from the blood by the blood handling system  10 .  
      Sensor  26  monitors for entrained air in the venous blood and comprises a sensor of the type described with respect to sensor  25 . Preferably, sensor  26  uses ultrasound to detect the presence of air entrained in venous blood, and is coupled to controller  33  so that an output of the sensor is used to evaluate one or more trigger conditions, as described hereinafter. Sensor  26  also may be used as a back-up to sensor  25  in the event sensor  25  fails. Sensor  27  may be any suitable pressure sensor such as a piezoelectric transducer or an electrostatic capacitance sensor, and is also coupled to controller  33  and provides an output corresponding to the pressure in venous line  13   a.    
      In operation, deoxygenated blood from the sterile field is routed through venous line  12  to blood inlet  41  of integrated blood processing component  31 . Blood entering gas collection plenum  50  is induced to circulate around the exterior of filter  56  until air or other gases entrapped in the blood separate out of the blood and collect in the upper portion of the gas collection plenum  50 . Responsive to the detection of the presence of a predetermined level or volume of gas by sensor  25 , controller  33  controls operation of valve  36  to evacuate the gas.  
      The gas removal system incorporated in the system of  FIGS. 1-3  is capable of removing large amounts of air from extracorporeal blood circuit  11  during initial startup, and may be used to displace the saline prime with the patient&#39;s blood thereby greatly reducing the amount of saline (or donor blood) returned to the patient from the prime of the system. Advantageously, this feature facilitates rapid and easy set-up of blood handling system  10 , as well as reduces the amount of hemodilution from saline delivered to the patient.  
      As blood circulates around filter  56  in central void  51 , it is drawn by the negative pressure head created by impeller  75  through filter material  59  and down through central void  51  into pump space  55 . Rotation of impeller  75  caused by drive unit  32 , under the control of controller  33 , propels blood up curved ramp  79  into blood inlet manifold  48 .  
      From blood inlet manifold  48 , the blood traverses blood oxygenation element  70  where it exchanges carbon dioxide and other gases for oxygen. Oxygenated blood then passes into blood outlet manifold  47 . Oxygenated blood then is directed back to the sterile field through arterial line  14 .  
       FIG. 5  depicts a preferred embodiment of a blood handling system suitable for implementing the automatic flow control features of the present invention. All blood, gas and electrical lines have been omitted for clarity from  FIG. 5 , and microprocessor-driven controller  33  (see  FIG. 1 ) and a back-up battery are enclosed in wheeled base  90 . Pole  91  is mounted in base  90 , and includes support arm  92  that supports blood processing component  31  on drive unit  32 . Support arm  92  also carries solenoid  93  that controls valve  36 , which is in turn coupled to suction source  34 . Pole  91  also carries support arm  93 , which carries display screen  95 . Screen  95  preferably is a touch-sensitive screen coupled to the controller, and serves as both an input device for the extracorporeal blood handling system  10  and a display of system function.  
       FIGS. 6A and 6B  provide representative samples of the information displayed on the main windows of the blood handling system  10 . As will of course be understood by one of ordinary skill in the art of computer-controlled equipment, the software used to program operation of the controller may include a number of set-up screens to adjust particular system parameters.  FIGS. 6A and 6B  are therefore the windows that will most commonly be displayed by the clinician during a procedure.  
      The display of  FIG. 6A  includes an indicator of battery status, a series of timers for pump operation, duration of cross-clamping, and an auxiliary timer, arterial and venous temperatures and pressures, the speed of centrifugal pump  55   a  and the corresponding blood flow rate. Preferably, controller  33  is programmed with a number of algorithms for determining an appropriate blood flow rate during the procedure, as determined based on body surface area (BSA). The window also may display the value of BSA determined by the selected algorithm based on the patient&#39;s dimensions, and the suggested blood flow rate.  
      The display of  FIG. 6B  includes much of the same information provided in the window of  FIG. 6A , but further shows temperatures and pressures graphically as well as numerically, so that the clinician can quickly identify trends in the data and take appropriate corrective measures. In addition, a lower portion of the windows displayed in  FIGS. 6A and 6B  may present system status or help messages, and include touch sensitive buttons that permit access to the other available functions.  
      Description of the Automatic Flow Control Systems of the Present Invention  
      In accordance with the principles of the present invention, microprocessor-based controller  33  of the extracorporeal blood handling system  10  of  FIG. 1  is programmed to provide at least one automatic flow control feature. More particularly, controller  33  is programmed to evaluate the outputs of sensor  25 ,  26  and  27  to evaluate the onset or existence of certain trigger conditions and to modulate system operation to avoid adverse impacts to system operation. In a preferred embodiment, modulation of system operation comprises regulating the speed of pump  55   a.    
      For example, the outputs of sensors  25 - 27  may detect non-negligible levels of gas in the blood and/or low venous pressure, and reduce the speed of pump  55   a  and the blood flow rate. These reductions are expected to increase the time available for a perfusionist to correct the trigger conditions. In addition, reducing pump speed lengthens the residence time of blood in filter  56 , thereby permitting air to be evacuated through valve  36  instead of being drawn through blood processing component  31  by pump  55   a.    
      In a first alternative embodiment, controller  33  may modulate a solenoid-driven clamp on the arterial line to selectively reduce flow rate through the system. The pressure increase in the arterial line created by partially occluding that line is transmitted back to the pump, thereby reducing blood flow through blood processing component  31 , and again lengthening the period of time available for the perfusionist to correct the trigger condition or for the trigger condition to resolve.  
      In yet another embodiment, controller  33  may modulate a solenoid-controlled valve on the priming circuit so that blood is shunted from arterial line  14  back to the inlet of blood processing component  31 . Once recirculation is established by opening the valve in the priming circuit, the flow rate through the arterial line will decrease. This decrease in flow will again provide needed time for the perfusionist to correct the trigger condition.  
      Referring again to  FIG. 1 , extracorporeal blood handling system  10  with automatic flow control includes extracorporeal blood circuit  11 , blood processing component  31 , and controller  33 . Preferably, the controller  33  includes a microprocessor having software including machine-readable instructions for interpreting sensor input and regulating pump speed and gas removal during automatic flow control.  
      According to one aspect of the present invention, controller  33  is electrically coupled to drive unit  32  of pump  55   a  and to sensors  25 - 27 . As disclosed above, the sensors are positioned within extracorporeal blood circuit  11  to detect the presence of air and/or measure venous pressure. Preferably, sensor  25  monitors the level of gas or blood in gas collection plenum  50 , sensor  26  detects the presence of gas or blood in venous line  12  and sensor  27  monitors the pressure in venous line  12 . When a trigger condition is detected, controller  33  modulates drive unit  32  to lower the speed of pump  55   a , thus lowering the blood flow rate through arterial line  14 .  
      Automatic flow control software is programmed to provide a reduction phase, a hold phase and a resume phase in response to a trigger condition. During the reduction phase, pump speed is reduced to lower the rate of blood flow through extracorporeal blood circuit  11 . Depending on the type and magnitude of the error condition, pump speed may be reduced by a fixed step, by a percentage of the initial pump speed or by rapidly dropping the pump speed to a predetermined lower limit. In addition, pump speed may be manually regulated.  
      After reducing the pump speed, the automatic flow control algorithm enters a hold phase, wherein pump speed is maintained at the lower level. In the hold phase, the perfusionist is prompted to enable the resume phase as soon as the trigger condition has been resolved. During the resume phase, pump speed is gradually increased back to the initial level.  
      The automatic flow control system includes algorithms to implement a number of different control modes of operation. The system preferably will not lower the pump speed below a predetermined lower limit, which is chosen so that forward blood flow is maintained through extracorporeal blood circuit  11  and to the sterile field.  
      In a preferred embodiment, the automatic flow control system includes a plurality of operational modes that respond to different trigger conditions, including a massive air detection mode, a discrete air detection mode, a bubble detection mode and a low venous pressure detection mode that can operate individually or in combination. These reduction modes are now be described with respect to  FIGS. 7-10 .  
      A first mode of operation is designed to handle the introduction of a large bolus of air into extracorporeal system  10 —the “massive air detection mode.” This is a high priority mode that is triggered when valve  36  (see  FIG. 1 ) is opened to remove a large amount of air from gas collection plenum  50 . Referring to  FIG. 7 , method  100  of automatic flow control is now described. At step  101 , controller  33  detects the opening of valve  36  in response to gas within gas collection plenum  50  (see  FIG. 1 ). At step  102 , controller  33  checks whether valve  36  remains open for a predetermined duration. If so, the first operational mode is triggered (step  104 ) and controller  33  reacts by rapidly dropping the pump speed to the predetermined lower limit (step  105 ). According to a preferred embodiment, the predetermined lower limit is 1800 RPM.  
      At step  106 , the automatic flow control enters the hold phase, wherein pump speed is maintained at the predetermined lower limit until the trigger condition is resolved (step  107 ) and the perfusionist enables the resume phase (step  108 ). During the resume phase, pump speed is gradually increased back to the initial level set by the perfusionist.  
      If valve  36  closes before the expiration of the predetermined duration, a second mode of operation—“the discrete air detection mode”—is triggered at step  103 . The discrete air detection mode is designed to handle the presence of discrete boluses of air in the venous blood. This is a medium priority mode that is triggered when valve  36  is briefly opened to remove discrete amounts of gas from the extracorporeal blood handling system  10 .  
      Referring to  FIG. 8 , method  110  of automatic flow control following detection of discrete quantities of air is described. At step  111 , valve  36  is opened to remove a discrete amount of gas from gas collection plenum  50  (see  FIG. 1 ). At step  112 , controller  33  checks whether valve  36  remains open for a predetermined minimum amount of time. If valve  36  remains open for more than the predetermined minimum amount of time, the massive air detection mode of  FIG. 7  is triggered at step  113 . The discrete air detection mode is triggered at step  114  if valve  36  closes before the predetermined amount of time has elapsed.  
      At step  115 , controller  33  reacts by rapidly dropping the pump speed by a predetermined percentage; the algorithm then enters a hold phase. In the hold phase, pump speed is maintained at the current level until either the trigger condition is resolved (step  117 ) or sensor  25  detects further discrete amounts of air, in which case the method proceeds to step  111 . After the trigger condition is resolved (step  117 ), the perfusionist enables the resume phase (step  118 ). In a preferred embodiment, the predetermined lower limit for the pump speed in the discrete air detection mode is 2500 RPM. If pump speed reaches this level, automatic flow control will remain in the hold phase (step  116 ) until the trigger condition is resolved (step  117 ) and the perfusionist enables the resume phase (step  118 ).  
      A third operational mode—“the bubble detection mode”—is designed to handle the presence of bubbles in the venous line. This is a medium priority mode, and is triggered when sensor  26  detects gas bubbles in venous line  12 . Referring to  FIG. 9 , method  120  of automatic flow control following bubble detection in venous line  12  is described. At step  121 , sensor  26  detects the presence of gas bubbles in venous line  12  (see  FIG. 1 ). At step  122 , controller  33  reacts by rapidly lowering the pump speed by a predetermined percentage. Next, controller  33  waits for a predetermined duration (step  123 ) before checking the status of sensor  26 . At step  124 , controller  33  determines whether sensor  26  continues to detect the presence of gas bubbles in venous line  12 . If gas bubbles remain in venous line  12 , the method proceeds to step  122 , wherein controller  33  further reduces pump speed by a predetermined percentage.  
      However, if the gas bubbles have dissipated, the automatic flow control system enters a hold phase at step  125 . In the hold phase, pump speed is maintained at the then-current level until the trigger condition has been resolved (step  126 ) and the perfusionist enables the resume phase (step  127 ). In a preferred embodiment, the predetermined lower limit for pump speed in the bubble detection mode is 2500 RPM. If pump speed reaches this level, automatic flow control will remain in the hold phase (step  125 ) until the trigger condition is resolved (step  126 ) and the perfusionist enables the resume phase (step  127 ). Alternatively, controller  33  may be programmed to enter the resume phase automatically if no further bubbles are detected within a predetermined time period.  
      A further operational mode—“the low venous pressure detection mode”—is designed to handle low venous pressure in venous line  12 . This is a low priority mode, and is triggered when sensor  27  detects low venous pressure in venous line  12 . Referring to  FIG. 10 , method  130  of automatic flow control following low venous pressure detection is described. At step  131 , sensor  27  detects that the venous line pressure has fallen below a predetermined threshold for a predetermined minimum duration. At step  132 , controller  33  reacts by lowering the pump speed by a predetermined increment. Next, controller  33  waits for a predetermined duration (step  133 ) to allow conditions to stabilize. Then, at step  134 , controller  33  determines whether sensor  27  continues to detect low venous pressure in venous line  12 . If venous pressure remains below the predetermined threshold, then the method proceeds to step  132  and controller  33  further reduces the pump speed by the predetermined increment.  
      If venous pressure is no longer below the predetermined value, automatic flow control algorithm enters a hold phase (step  135 ). In the hold phase, pump speed is maintained at then-current level until the trigger condition is resolved (step  136 ) and the perfusionist enables the resume phase (step  137 ). In a preferred embodiment, the predetermined lower limit for pump speed in the low venous pressure detection mode is 1800 RPM. If pump speed reaches this level, automatic flow control will remain in the hold phase (step  135 ) until the trigger condition is resolved (step  136 ) and the perfusionist enables the resume phase (step  137 ). Controller  33  also may be programmed to enter the resume phase automatically when the pressure in venous line  12  is detected to exceed a preset level for a predetermined time period.  
      In the event that multiple reduction modes are triggered at the same time, the highest priority mode will take precedence. According to a preferred embodiment, the massive air detection mode is the highest priority mode followed by the discrete air detection mode, the bubble detection mode and the low venous pressure detection mode. In cases where a lower priority mode is interrupted by a higher priority mode, control returns to the lower priority mode only after the trigger condition causing the higher priority mode has been resolved. By way of example, if discrete air is sensed by sensor  25  during low venous pressure detection mode, then the automatic flow control system automatically switches to the discrete air detection mode. After the discrete air detection mode trigger condition (i.e., the presence of discrete amounts of air in the gas collection plenum) has been resolved, automatic flow control automatically returns to the low venous pressure detection mode.  
       FIG. 11A  is an illustrative display of main screen  140 , similar to  FIG. 6 , that incorporates the automatic flow control system of the present invention. As will be understood by one of ordinary skill in the art of computer-controlled equipment, the software used to program operation of controller  33  may include a number of set-up screens to adjust particular system parameters.  FIG. 11A  depicts screen  140  that will most commonly be displayed by the perfusionist during automatic flow control.  
      As shown in  FIG. 11A , main screen  140  includes a series of timers for pump operation, duration of cross-clamping, and a cardioplegia timer, arterial and venous temperatures and pressures, as measured, for example, at the blood inlet and blood outlet of the blood processing component  31 , the speed of the centrifugal pump (RPM) and the corresponding blood flow rate.  
      Controller  33  preferably is programmed with a number of algorithms for determining appropriate blood flow rates and pump speeds during the procedure and for evaluating the outputs of sensors  25 - 27  in accordance with methods  100 ,  110 ,  120  and  130  described hereinabove. Controller  33  also preferably includes storage that is programmed with default values for the pump speed limit values, sensor threshold values, and time periods for invoking and exiting the various operational modes. Alternatively, these values may be computed based on target flow rate values computed, for example, based on the patient&#39;s BSA value, or these values may be input directly via an alpha-numeric display mode of screen  140  (not shown).  
      In addition, a portion of main screen  140  includes touch sensitive buttons that permit access to the other available functions. More particularly, main screen  140  includes button  141  for manually overriding automatic flow control. With this feature, a perfusionist may at any time disable or partially disable the automatic flow control system by pressing button  141 . Button  141  functions both as a system control and a prominent indicator of the automatic flow control status. To increase its visibility to a perfusionist, button  141  preferably is optionally located in the region of screen  140  that includes pump speed and flow values.  
      As illustrated in  FIG. 11B , button  141  preferably has three states including an enabled state (“AFC ENABLED”) which responds to all trigger events, a partially disabled state (“AFC NO Pven”) which does not respond to low venous line pressure and a disabled state (“AFC DISABLED”). Optionally, button  141  includes different shades or colors as a further visual indication of automatic flow control system status. According to a preferred embodiment, button  141  has a green tint to indicate that automatic flow control is enabled, a yellow tint to indicate automatic flow control is partially disabled and a red tint to indicate automatic flow control is disabled.  
      Referring again to  FIG. 11A , main screen  140  also includes button  142  to be used after resolving the trigger condition(s). Pressing button  142  gradually increases pump speed back to the initial level (i.e., the pump speed at which the first trigger condition occurred). Optionally, button  142  is darkened when pump speed returns to the initial level and/or when automatic flow control is re-triggered.  
      The system also optionally includes knob  143  for manually controlling the flow rate within the extracorporeal blood circuit  11 . Activating (i.e., turning) knob  143  immediately returns blood handling system  10  to normal operation and darkens button  142 . Using knob  143 , a perfusionist may manually control how quickly the pump speed and flow rate are returned to their initial levels following automatic flow control.  
      Main screen  140  further may include status bar  144  to present system status and/or help messages. These messages are optionally displayed on the display unit during reduction and hold phases to indicate the present mode or modes of operation. As shown in  FIG. 11A , status bar  144  indicates that automatic flow control was enabled due to a combination of the presence of discrete air in the system and low venous pressure. However, since these trigger conditions have cleared, button  142  is available. The status messages are removed if button  142  is pressed or knob  143  is activated. When button  142  is pressed, the message “AFC Resuming RPM” is displayed.  
       FIGS. 12A and 12B  are illustrative graphs showing how the automatic flow control system responds to various triggers over time. For exemplary purposes, actual values for variables such as pressure, pump speed and time, are described below in parentheses.  
       FIG. 12A  is a graph depicting how the automatic flow control system responds over time to a low venous pressure trigger. Initially, venous pressure drops briefly below a predetermined threshold (−100 mmHg), but not for a predetermined minimum duration (2 sec). Thus, the low venous pressure detection mode is not triggered. Thereafter, venous pressure drops below the predetermined threshold (−100 mmHg) for a duration exceeding a predetermined minimum duration (2 sec) and the low venous pressure detection mode is triggered. The automatic flow control algorithms cause the pump speed to be reduced by a predetermined increment (e.g., 300 RPM) from 4000 to 3700 RPM. After waiting for a predetermined period of time (1 sec), the venous pressure is evaluated by controller  33  using the output of sensor  27 , and is determined still to be below the predetermined threshold (−100 mmHg). Thus, pump speed is again reduced by the predetermined increment (300 RPM) from 3700 to 3400 RPM.  
      After waiting for an additional period of predetermined duration (e.g., 1 sec), the venous pressure is again evaluated, and the pump speed is reduced for a third time by the predetermined increment (300 RPM) from 3400 to 3100 RPM. This time, when venous pressure is evaluated, it is above the predetermined threshold (−100 mmHg). The automatic flow control system now enters the hold phase, in which the pump speed (3100 RPM) is maintained until the perfusionist can resolve the trigger condition. After resolving the trigger condition, the venous pressure increases (to −60 mmHg) and the perfusionist presses button  142  to signal automatic flow control to begin the resume phase. During the resume phase, pump speed is increased non-linearly over a period of time (5-6 sec) to the initial level (4000 RPM).  
       FIG. 12B  is a graph depicting how the automatic flow control system responds over time to the detection of various amounts of air in the extracorporeal blood handling system  10 . As shown in  FIG. 12B , the automatic flow control system initially responds to a discrete air trigger and then responds to a massive air trigger. At the outset, valve  36  opens momentarily. Since valve  36  remains open for less than a predetermined duration (¼ sec), the discrete air detection mode is triggered instead of the massive air detection mode. The automatic flow control system rapidly decreases pump speed by a predetermined percentage (by 30% of initial RPM=4000×3=1200 RPM) to a new level (4000 RPM−1200 RPM=2800 RPM). Then, automatic flow control begins a hold phase at the new pump speed (2800 RPM). Next, valve  36  again opens momentarily for less than the predetermined duration (¼ sec) triggering another rapid reduction in pump speed by the predetermined percentage (by 30% of 2800 RPM=840 RPM) toward a new level (2800 RPM−840 RPM=1960 RPM).  
      However, before reaching the new level (1960 RPM), the pump speed hits the predetermined lower limit speed (2500 RPM) and automatic flow control begins a hold phase at the predetermined lower limit pump speed (2500 RPM). When valve  36  again opens momentarily for less than the predetermined duration (¼ sec), pump speed stays at the lower limit value (2500 RPM). Once the perfusionist corrects the problem and presses button  142 , pump speed is increased non-linearly over a period of time (5-6 sec) to the initial level (4000 RPM).  
      Subsequently, valve  36  again opens, but this time for greater than the predetermined duration (¼ sec) and the massive air detection mode is triggered. In this case, the automatic flow control system rapidly reduces the pump speed to the predetermined lower limit for this mode of operation (1800 RPM).  
      Referring now to  FIG. 13 , an alternative embodiment of an automatic flow control system in accordance with the principles of the present invention is described. Blood processing system  150  includes all of the components blood processing system  10  described in  FIG. 1 , including microprocessor-based controller  33 . Unlike the embodiment of the automatic flow control system described above with respect to  FIGS. 7-12 , the automatic flow control system of  FIG. 13  uses solenoid-controlled pinch valve  151 , or other suitable valve, to restrict flow to arterial line  14 , rather than relying on modulation of the pump speed.  
      Valve  151  is coupled to controller  33 , and is activated by controller  33  responsive to outputs generated by sensors  25 ,  26  and  27 . Controller  33  may be programmed with multiple operational modes, as described hereinabove, and selectively restricts the flow through arterial line  14 , either with or without pump speed modulation. For example, in a discrete air detection mode, controller  33  activates valve  151  to constrict the flow diameter by a predetermined percentage (e.g., 50%). This constriction reduces flow through the arterial line, and creates a backpressure that reduces the output flow rate of the centrifugal pump. This reduction in flow rate through the pump consequently extends the residence time of blood flowing through filter  56  and gas collection plenum  50  (see  FIG. 3 ), and thereby enhances the ability of the gas removal system to evacuate gas from the blood processing system.  
      As another example, controller  33  may be programmed with algorithms that provide a massive air detection operational mode, in which valve  151  is actuated to reduce the flow rate through arterial line by 80%. In addition, the controller also may reduce the pump speed, thereby extending the time during which the perfusionist can correct the trigger condition and avoid de-priming of the blood processing component  31 . Controller  33  may be programmed to modulate valve  151 , either alone or in conjunction with pump speed, to implement strategies for handling the presence of bubbles or low pressure in venous line  12 .  
      Referring to  FIG. 14 , a further alternative embodiment of an automatic flow control system in accordance with the principles of the present invention is described. Blood processing system  160  includes all of the components blood processing system  10  described in  FIG. 1 , including microprocessor-based controller  33 . Unlike the previously-described embodiments of the automatic flow control system, the automatic flow control system of  FIG. 14  uses solenoid-controlled pinch valve  161 , or other suitable valve, to selectively open a recirculation loop using the priming circuit.  
      Valve  161  is coupled to controller  33 , and is activated by controller  33  responsive to outputs generated by sensors  25 ,  26  and  27 . Controller  33  may be programmed with multiple operational modes, as described hereinabove, and selectively opens a bypass or recirculation loop between the outlet and inlet of blood processing component  31 . Valve  161  may be used either alone, or in conjunction with modulation of pump speed, arterial line constriction, or both.  
      For example, in a discrete air detection mode, controller  33  activates valve  161  to fully open valve  161  from either a partially or completely closed configuration. The creation of a bypass flow path reduces flow through the arterial line, and preferentially shunts the output of the centrifugal pump to the inlet of blood processing component  31 . The reduction in flow rate to the arterial line reduces the risk of perfusing air-laden blood to the patient. Moreover, recirculating the blood to the inlet of blood processing component  31  consequently extends the residence time of blood flowing through filter  56  and gas collection plenum  50  (see  FIG. 3 ), and enhances the ability of the gas removal system to evacuate gas from the blood processing system.  
      Controller  33  also may be programmed with algorithms that provide a massive air detection operational mode, in which valve  161  is actuated to bypass a substantial portion of the blood flow at the outlet of blood processing component  31  to the inlet of component  31 . In addition, the controller also may reduce the pump speed, and actuate valve  151  (if present) to extend the time during which the perfusionist can correct the trigger condition and avoid de-priming of the blood processing component  31 . Controller  33  may be programmed to modulate valve  161 , either alone or in conjunction with pump speed, to implement strategies for handling the presence of bubbles or low pressure in venous line  12 .  
      Although preferred illustrative embodiments of the present invention are described above, it will be evident to one skilled in the art that various changes and modifications may be made without departing from the invention. It is intended in the appended claims to cover all such changes and modifications that fall within the true spirit and scope of the invention.