Abstract:
An bolus delivery system includes an implantable pump, a sensor for sensing an adverse patient condition, such as atrial fibrillation, and a catheter for delivery of a bolus of drug to a target area of a living body. The pump is provided with a bolus metering assembly which includes, in a preferred embodiment, an auxiliary bellows defining a bolus reservoir in addition to the main reservoir of the pump. The auxiliary bellows is selectively placed in fluid communication with the pressurized main supply of drug via an inlet valve to refill the bolus reservoir. An outlet valve is provided to permit egress of the bolus to the catheter from the bolus reservoir. A drive train including a stepper motor and a face cam selectively opens and closes the inlet and outlet valves to effect accumulation or metering and delivery of the bolus. The auxiliary bellows is preferably provided as a collapsible element resiliently biased to an expanded position and is collapsed under pressure in the main reservoir to expel the bolus.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to implantable devices for delivering beneficial agents or drugs to a living body. More particularly, the present invention relates to implantable devices for metering and delivering a drug bolus to a target area in a living body in response to sensed adverse patient conditions. 
     2. Description of the Related Art 
     Cardiac arrhythmias, which are irregularities in cardiac rhythms, adversely affect millions of individuals. Atrial fibrillation is likely the most common cardiac arrhythmia and may result in dizziness, weakness and other adverse effect. Moreover, atrial fibrillation, may result in death if it leads to ventricular fibrillation. Accordingly, significant efforts have been undertaken to provide therapy to prevent or relieve atrial fibrillation. Such efforts have included drug therapy, in the form of oral or intravenous drugs, and electrical defibrillation techniques. 
     Implantable systems are known for detecting the onset of fibrillation and providing a patient with electronic countermeasures. For example, U.S. Pat. No. 5,817,131, which is incorporated herein by reference in its entirety, discloses an implantable atrial defibrillators which includes implements for monitoring electrical activity of the heart and providing cardioversion countermeasures as well as pain relief therapy to the central nervous system in response to detection of the onset of atrial fibrillation or other adverse conditions. 
     There is a current trend towards the use of implantable drug delivery systems to provide site-specific and/or sustained delivery of beneficial agents to address adverse patient conditions, such as atrial fibrillation. Such delivery systems may include implantable infusion pumps, which typically include a pressurized drug reservoir and some form of fluid flow control. One example of an implantable infusion pump is the SYNCHROMED™ pump manufactured by Medtronic, Inc. of Minneapolis, Minn. 
     In atrial defibrillation applications, drug delivery systems must be capable of rapidly and accurately metering and delivering one or more drug boluses to a target area in response to the detection of an adverse condition, such as atrial fibrillation. Known drug infusion pumps, however, are not adapted to rapidly meter and deliver such drug boluses. There is thus a need for an implantable infusion pump which is capable of rapidly and accurately metering and delivering one or more boluses of drug in response to a detected adverse condition. 
     SUMMARY OF THE INVENTION 
     The present invention solves the aforementioned problems and others by providing an implantable pump which is capable of metering a drug bolus and delivering a drug bolus in response to a detected condition of atrial fibrillation. In a preferred embodiment, an implantable pump is provided with a control module which processes incoming signals from sensors to detect the onset of an adverse, patient condition. The pump is provided with a bolus metering assembly which is driven by a drive train in response to command signals from the control module. The bolus metering assembly includes an inlet valve which is adapted to permit ingress of pressurized drug-containing fluid from a pressurized main bellows reservoir into a collapsible auxiliary bellows that defines a bolus reservoir. An outlet valve is also provided to permit egress of the bolus of drug from the bolus reservoir after an appropriate amount of drug has accumulated therein. The inlet and outlet valves are driven by valve tappets, which are driven by a face cam, that provides the proper timing sequence for opening and closing the inlet and outlet valves. According to one aspect of the invention, the auxiliary bellows defining the bolus reservoir is exposed to the pressure in the main reservoir such that pressure in the main reservoir is used to expel the bolus of drug from the bolus reservoir. 
     In another embodiment, the bolus metering assembly is provided with a flow restrictor instead of an inlet valve. A cam drives the outlet valve to permit egress from the bolus reservoir after a predetermined amount of drug-containing fluid has flowed through the inlet restrictor. An auxiliary valve is provided within the auxiliary bellows reservoir and is adapted to engage an outlet port and abruptly stop the egress of the bolus when the auxiliary bellows is fully collapsed. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The invention will be described with reference to the drawings, which form a part of this specification. Those of ordinary skill will understand that the invention is not intended to be limited to the exemplary embodiments illustrated in the drawings, of which: 
     FIG. 1 is an illustration of an implanted drug delivery system incorporating a pump including a bolus delivery system according to a preferred embodiment of to the present invention; 
     FIG. 2 is a block diagram of a bolus delivery system according to a preferred embodiment of the invention; 
     FIG. 3 is an exploded view of a pump according to a preferred embodiment of the present invention; 
     FIG. 4 is a cross-section taken along lines  4 — 4  of FIG. 3; and 
     FIG. 5 is a cross-section of a pump including a bolus delivery system according to another preferred embodiment of the present invention. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring to FIG. 1, a bolus drug metering system according to the present invention comprises generally a bolus metering pump  10  which communicates with a drug delivery catheter  11  which is implanted in the tissue of a human heart  2  for delivering a beneficial agent or drug thereto. Also implanted in the tissue of the human heart is a sensing lead  3  which is adapted to sense electrical conditions at a specific location in the human heart to thereby detect the onset of atrial fibrillation. Sensing lead  3  communicates signals to pump  10  and processing circuitry which is described in U.S. Pat. No. 5,817,131, referenced above. Sensing lead  3  is preferably a contact type of lead for sensing atrial fibrillation. 
     Referring now to FIG. 2, a bolus delivery system  5  according to a preferred embodiment of the present invention comprises generally a programmer  40  which provides signals to a radio frequency (RF) transmitter  42 , which, in turn, provides radio signals to an RF receiver  44  onboard the implanted pump  10 . As an example, programmer  40  may comprise a modified Medtronic Model No. 9790 programmer with atrial defibrillation software. RF receiver  44  provides signals to control module  46  which may be a microprocessor based computer onboard the pump  10  and which may be provided with instructions for processing data received from indication sensors  50 . For example, the Medtronic Model 7250 atrial defibrillator hybrid which incorporates atrial fibrillation detection algorithms may be used for sensor signal processing and operation of the pump motor for drug delivery when fibrillation is detected. 
     Control module  46  provides signals to an acoustic transducer  48  which is used to produce an:audible signal to alert the patient that sensed conditions indicate the onset of atrial fibrillation. Indication sensors  50  may include the sensing lead  3  and other implanted sensing devices in the human body. An onboard power supply  52 , for example a Medtronic PROMEON™ battery may be used to power the device. 
     Control module  46  provides signals to a pump drive train  150  which in turn drives the bolus metering assembly  100 , the operation of which will be explained in detail below. Bolus metering assembly receives drug from a pressurized reservoir  20  and supplies drug in metered dosages to the output catheter  11  which delivers the drug to the body of the patient. Preferably, the pump drive train  150  comprises a motor and driving components similar to those used on the SYNCHROMED model pump manufactured by Medtronic, Inc. 
     Referring now to FIGS. 3 and 4, the bolus metering pump  10  according to a preferred embodiment of the invention comprises generally a pump body which encloses a pressurized main reservoir  20  which is in fluid communication, via drug outlet passage  30 , with a bolus metering assembly  100 . Bolus metering assembly  100  generally comprises an inlet valve  160 , an outlet valve  170 , and a bolus storage chamber  180 . 
     The implantable pump  10  includes a back shield  12 , and a top shield  14  and a bulkhead  16 . The back shield  12  and bulkhead  16  enclose the main reservoir  20 . An open end of bellows  18  is fastened at to the bulkhead  16  in a known manner. As will be recognized by those of ordinary skill, bellows  18  is manufactured as an expandable and collapsible element. Main reservoir  20  is typically provided with a main supply of drug and pressurized by a propellant, typically a fluorocarbon, which occupies the space between the bellows  18  and the pump backshield  12  and which maintains a constant pressure or gas-spring on the bellows  18 . A refill port  22  is provided for permitting refill of the main reservoir  20  with a desired drug and comprises a septum  24  for sealably receiving a hypodermic needle (not shown) for providing a refill supply of the desired drug to the reservoir  20 . 
     Bulkhead  16  includes the main reservoir drugs outlet passage  30  in fluid communication with the interior of bellows  18  to convey drug from the main reservoir  20  to the bolus metering assembly  100 . Preferably, a bacteriostatic filter  32  is provided upstream of outlet passage  30  to prevent the introduction of harmful bacteria into the bolus supply of drug. Main reservoir drug outlet passage  30  communicates with the inlet valve  160 . It will be recognized that the drawing in FIG. 4 shows a portion of the main reservoir drug outlet passage  30  that is hidden in the drawings by the refill port  22 . 
     Inlet valve  160  includes an inlet valve inlet port  162  and an inlet valve outlet port  167 , both of which may be sealed by an inlet valve seal  166  when it rests in a sealing position (shown in FIG. 4) on an inlet valve seat  164 . An inlet valve diaphragm  168  is provided to isolate the inlet valve seal  166  and the drug flowing therein from the pump drive train  150 . Diaphragm  168 , which is pressurized on its interior, by the pressurized drug in a bolus storage chamber  180  provides an upward bias on the inlet valve seal  166 . The inlet valve  160  is actuated via an inlet valve tappet  167  which is operated by a generally circular face cam  154 , which is shown in cross-section in FIG. 4 as having typical cam raised and lowered portions. 
     Inlet valve outlet port  161  is in fluid communication with a bolus storage chamber  180  which is defined by the interior of a round auxiliary bellows  182 . Auxiliary bellows  182  is provided as a deformable element which is biased towards its expanded position, for example, by construction of a material that elastically deforms, but does not yield, as bellows  182  travels from its expanded position to its collapsed position. A stop member  184  encircles the auxiliary bellows  182  and limits its expansion. 
     The interior of auxiliary bellows  182  and therefore the bolus storage chamber  180  are in fluid communication with an outlet valve  170 . The outlet valve  170  includes an outlet valve inlet port  172  to permit the ingress of fluid from the bolus storage chamber  180 . Outlet valve  170  also includes an outlet valve outlet port  177  which is in communication with pump outlet  190  and a catheter port  192  to permit the egress of fluid from the outlet valve  170  for delivery of a drug to a catheter (as seen in FIG.  1 ). Both outlet valve inlet port  172  and outlet valve outlet port  177  may be sealed by the outlet valve seal  176  when the cam face  154  is rotated to a selected position by the drive train  150 . Like inlet valve  160 , outlet valve  170  is also provided with a diaphragm  178  for sealing the outlet valve seal  176  and the outlet valve seat  174  and for providing an upward bias on the outlet valve seal  176 . 
     The drive train  150  includes drive train stepper motor  152  which rotates the face cam  154  to cause reciprocal movement of the inlet valve tappet  167  and a similar outlet valve tappet  156 . As will be recognized by those of ordinary skill, face cam  154  is provided with contoured surfaces to cause appropriate motion and timing of the opening and closing of the inlet valve  160  and outlet valve  170 . The valve tappets  167  and  156  in turn actuate the inlet and outlet valve seals  166  and  176  to provide for the ingress of drug into the bolus storage chamber  180  and the subsequent egress of the bolus from the bolus storage chamber  180 . 
     In operation, the bolus storage chamber  180  is first filled in the following manner. Face cam rotates to a position in which the inlet valve  160  is open and thereby the inlet valve seal  166  is removed from the valve seat  164  to permit the passage of drug from the main reservoir outlet passage  30  into the bolus storage chamber  180 . Those of ordinary skill will recognize that drug will flow from the main reservoir  20  into the bolus storage chamber  180  as a result of the drug being under presure in the main reservoir  20  and as a result of the resilient bias on the auxiliary bellows  182  to expand to the expanded position shown in FIG. 4 where the outer periphery of auxiliary bellows  182  contacts the stop member  184 . This action is much the same as the tendency of a medicine dropper bulb to return to its undeformed position after deformation. As the face cam  154  continues to rotate, inlet valve  160  will close to prevent further ingress of drug into the bolus storage chamber  180 . Closure of the inlet valve  160  also isolates the pressure within the main bellows reservoir  20  from the interior of the auxiliary bellows  182 . After closure of the inlet valve  160 , continued rotation of face cam  154  results in opening of the outlet valve  170 , thus permitting the egress of the accumulated drug within the bolus storage chamber  180  into the catheter port  192 . It will be recognized that the opening of outlet valve  170  will permit the escape of drug from bolus storage chamber  180 , the impetus for which is provided by the exposure of the bolus storage chamber  180  to a lower pressure namely that in the catheter″. Thus, the auxiliary bellows  182  will collapse under the pressure from the drug in the main reservoir  20  with the resulting expulsion of drug into the catheter port  192  through the catheter″, and ultimately to the heart  2 . Further continued rotation of the face cam  154  results in closure of the outlet valve  170  and later, reopening of the inlet valve  160  to permit the ingress of another dose of drug into the auxiliary bellows  182 . Delivery of drug may then be repeated for another episode of atrial fibrillation if needed. 
     It will be recognized by those of ordinary skill that other mechanical implements besides those described above may be used to control the inlet and outlet valves. For example, face cam  154  and tappets  167  and  176  may be replaced by radial acting cams, groove acting cams, roller cams, or other linkage systems. In addition, it will also be recognized by those of ordinary skill that the reservoirs and dosing chambers construction may be comprised of metal, plastic or ceramic materials. 
     FIG. 5 illustrates a cross section of another preferred embodiment of the present invention. In this embodiment, the inlet valve  160  of the aforementioned embodiment is replaced with a flow restrictor  260  and a valve seal  262  provided on an interior surface of the auxiliary bellows  182  and positioned to engage outlet valve inlet port  172  when auxiliary bellows  182  is in its collapsed position. According to this embodiment, refill of the bolus storage chamber  180  proceeds in the following manner. The auxiliary bellows  182 , after collapsing, will cause the valve  262  to seal off the outlet valve inlet port  172  and prevent further egress of drug from the interior of auxiliary bellows  182 . Drug continues to flow from the main reservoir  20  through the main reservoir outlet passage  30 , through the flow restrictor  260  and into the bolus storage chamber  180  at a predetermined rate. Thus, the auxiliary bellows  182  will be refilled with a supply of drug. When fibrillation is detected, the control module will activate the motor  152  of the drive train  150  thereby causing the outlet valve  170  to open and permit the flow of the bolus into the outlet catheter port  192 . During delivery of the bolus, the restrictor  260  functions as a virtually closed valve due to its low flow rate and the relatively high flow rates out through the outlet valve  170  and catheter port  192 . The seal  262  on the interior of auxiliary bellows  182  functions to abruptly stop flow of drug from the bolus reservoir  180  and to thereby provide precise control of the metered amount of drug. 
     Although the preferred embodiment of this invention has been described above in some detail, it should be appreciated that a variety of embodiments will be readily apparent from the foregoing description to persons of ordinary skill. For example, it will be recognized that more than one bolus metering assembly may be provided on a single pump, to permit rapid successive delivery of more than one drug bolus, when needed. The description is intended to be illustrative of the preferred embodiment of this invention and not intended to be limiting to the scope of protection sought by the applicants, which scope is defined by the appended claims.