U.S. patent application number 09/811685 was filed with the patent office on 2002-09-19 for closed loop drug delivery system and remote management thereof.
This patent application is currently assigned to Medtronic, Inc.. Invention is credited to Thompson, David L..
Application Number | 20020133196 09/811685 |
Document ID | / |
Family ID | 25207256 |
Filed Date | 2002-09-19 |
United States Patent
Application |
20020133196 |
Kind Code |
A1 |
Thompson, David L. |
September 19, 2002 |
CLOSED LOOP DRUG DELIVERY SYSTEM AND REMOTE MANAGEMENT THEREOF
Abstract
A transdermal drug delivery device in communication with at
least one IMD is externally mounted to deliver pain analgesics
and/or threshold reduction medicants prior to or contemporaneous
with a shock associated with a pacer, a defibrillator and similar
therapy device. The drug delivery device includes an attachable
strip with a storage for medicants and is epidermally mounted. The
medicants are released into the bloodstream in response to an
indication that the IMD is about to deliver a shock. The drug
delivery device is adapted for use with various drugs. Further, the
delivery of drugs could be controlled by the patient to provide a
semi-automatic use and/or to terminate delay shock. The transdermal
drug delivery device and the IMD include system status indicators
to provide real-time operational data of the drug delivery device
and the IMD individually and in combination. The drug delivery
device is also implemented with a CHF monitor to treat CHF
patients.
Inventors: |
Thompson, David L.;
(Andover, MN) |
Correspondence
Address: |
MEDTRONIC, INC.
710 MEDTRONIC PARKWAY NE
MS-LC340
MINNEAPOLIS
MN
55432-5604
US
|
Assignee: |
Medtronic, Inc.
|
Family ID: |
25207256 |
Appl. No.: |
09/811685 |
Filed: |
March 19, 2001 |
Current U.S.
Class: |
607/3 |
Current CPC
Class: |
A61N 1/3956 20130101;
A61N 1/30 20130101 |
Class at
Publication: |
607/3 |
International
Class: |
A61N 001/362 |
Claims
What is claimed is:
1. A drug delivery strip in communication with an implanted medical
device (IMD), the combination comprising: means for monitoring at
least one pretherapy event in the IMD; means for communicating to
the drug delivery strip that said at least one pretherapy event is
eminent; and means for activating the delivery of drugs from the
drug delivery strip prior to or contemporaneous with a therapy
resulting from said at least one pretherapy event.
2. The combination of claim 1 wherein said therapy event includes
the delivery of cardioversion defibrillation energy.
3. The combination of claim 1 wherein said therapy event includes
the delivery of energy shock to the heart.
4. A transdermal drug delivery device in wireless communications
with at least one implanted medical device (IMD) wherein the drug
delivery device is externally mounted to deliver pain analgesics
and/or threshold reduction medicants prior to a shock associated
with a pacer, a defibrillator and similar therapy device, the drug
delivery device comprising: means for storing the medicants; means
for mounting epidermally to a patient; means for communicating with
at least one IMD; and means for releasing the medicants
transdermally responsive to at least one indication that the at
least one IMD is about to deliver the shock.
5. A transdermal drug delivery device in combination with an IMD to
deliver medicants to a CHF patient, the combination comprising: the
drug delivery device externally mounted on a patient; the IMD being
a CHF monitoring device; and a communication system between the
drug delivery device and the IMD to enable the delivery of the
medicants prior to or contemporaneous with CHF signals from the
IMD.
6. The combination of claim 5 wherein said signals include
parameters that lie outside a pre-selected range of cardiac
events.
7. A drug delivery device in communication with an IMD to deliver
specialty drugs responsive to signals from the IMD relating to
cardiac conditions and/or therapy, the drug delivery device having
storage for the specialty drugs, the drugs comprising: opiates;
non-opiates; defibrillation threshold reducing agents; and agents
for treatment of CHF.
8. The drug delivery device of claim 7 wherein said opiates include
morphine sulfate and hydromorphine.
9. The drug delivery device of claim 7 wherein said non-opiates
include alpha-2 adreneorgic agonists and neuron specific calcium
channel blocking agents.
10. The drug delivery device of claim 7 wherein said defibrillation
threshold reducing agents include D-salotol, Procainamade or
Quinidine as alternatives or in combination with one or both said
opiates and said non-opiates.
11. The drug delivery device of claim 7 wherein said agents for
treatment of CHF includes captopril, enalapril, lisinopril and
quinapril.
12. The drug delivery device of claim 7 wherein said specialty
drugs include drugs designed to overcome pain and threshold
associated with cardiac shock.
13. The drug delivery device of claim 7 wherein said specialty
drugs include drug types designed to treat CHF conditions.
14. The drug delivery device of claim 13 wherein the drug types are
suited to treat pain, threshold, and CHF conditions in combination
thereof.
15. A drug delivery device in cooperation with an IMD forming a
system in which one or more drugs are discharged into a patient
based on signals received from the IMD, the system comprising: a
communication link between the drug delivery device and the IMD;
automatic means for discharging the one or more drugs into the
patient when the signals are received from the IMD via said
communication link; and automatic means for terminating the
discharge of the one or more drugs.
16. The system of claim 15 wherein a semi-automatic means for
discharging is implemented to enable the patient to activate the
drug discharge on an as-needed basis.
17. The system of claim 15 wherein a semi-automatic means for
terminating the discharge is implemented to enable the patient to
terminate the drug discharge on an as-needed basis.
18. The system of claim 15 wherein the communication link includes
system status indicators.
19. The system of claim 15 wherein said system status indicators
include visual displays.
20. The system of claim 15 wherein said system status indicators
include audible signals.
21. The system of claim 15 wherein said system status indicators
include tactile interfaces.
22. The system of claim 15 wherein the communication link includes
override means to enable the patient to terminate or delay shock
using the drug delivery device as a controller.
23. The system of claim 15 wherein the communication link includes
remote monitoring and programming means to enable remote patient
management.
Description
FIELD OF THE INVENTION
[0001] The present invention generally relates to medical devices.
Specifically, the invention relates to communication between an
implanted medical device and an external drug delivery device in
wireless data communication thereof. More specifically, the
invention relates to a system that automatically delivers analgesic
and/or threshold reduction medications prior to the application of
cardiac shock or drug delivery for pulmonary hypertension, for
example, using RV pressure. The release of the drug is coordinated
between the implanted device and the external device via the
wireless communication system. The invention also provides remote
management of a patient wherein drug delivery data from the
external device and therapy information from the implanted device
are transferred to a remote location using various methods of data
transfer to enable physicians and caregivers to remotely review and
monitor the patient as needed. In one aspect of the present
invention, the drug delivery dose and frequency of treatment are
preferably controlled via parametric modifications and adjustments
of the implanted medical device. In yet another embodiment, the
external drug delivery device is directly programmed overriding
communication signals that initiate and call for drug delivery from
the implanted medical device.
BACKGROUND OF THE INVENTION
[0002] Current practice of implanting both a therapeutic medical
device such as a cardiac pacemaker, defibrillator, etc., in
conjunction with implantable drug pumps is cumbersome and expensive
to manage. Further, for example, with a defibrillator and an
implanted drug delivery device, one would need to run a catheter to
deliver the drug in addition to leads for the defibrillator. Most
implanted drug delivery devices known in the art, do not deliver
drugs directly into the bloodstream.
[0003] The alleviation of cardioversion shock pain has been the
subject of various patents in the prior art. Most of the
pain-alleviating therapy, in conjunction with the delivery of
cardioversion energy to the heart chamber is well known in the art.
Further, the alleviation of pain through the operation of
implantable drug dispensers for automatically, periodically,
delivering a bolus of a pain-alleviating drug at the site in the
body are also well known in the art. For example, U.S. Pat. Nos.
5,662,689 and 5,817,131 to Elsberry et al, disclose a methods and
apparatus for alleviating cardioversion shock pain. The disclosures
include an implantable cardioverter for providing cardioversion
electrical energy to at least one chamber of a patient's heart in
need of cardioversion and applying a pain alleviating therapy at an
appropriate site in the patient's body prior to, or in conjunction
with, the delivery of the cardioversion energy to the heart chamber
to alleviate propagated pain perceived by the patient. The combined
cardioversion and pain alleviating therapies are preferably
realized in a single implantable, multi-programmable medical device
or separate implantable cardioversion and pain control devices with
means for communicating operating and status commands between the
devices through the patient's body.
[0004] U.S. Pat. No. 5,893,881 issued to Elsberry et al discloses a
method and apparatus for alleviating cardioversion shock pain by
delivering a bolus of analgesic. Specifically, the invention
discloses an implantable cardioverter for providing cardioversion
electrical energy to at least one chamber of a patient's heart in
need of cardioversion and applying a pain alleviating therapy at an
appropriate site in the patient's body prior to or in conjunction
with the delivery of the cardioversion energy to the heart chamber
to alleviate propagated pain perceived by the patient. The combined
cardioversion and pain alleviating therapies are preferably
realized in a single implantable, multiprogrammable medical device
or separate implantable cardioversion and pain control devices with
means for communicating operating and status commands between the
devices through the patient's body.
[0005] U.S. Pat. No. 5,087,243 to Avitall discloses a myocardial
iontophoresis device. An implantable iontophoretic delivery system
for use in applying medicinal materials rapidly to specific
subcutaneous tissue sites of interest in conjunction with an
implanted defibrillator is disclosed which uses a subcutaneously
situated pouch for supplying medication in conjunction with a pair
of defibrillator electrodes connected to a power source. One of the
electrodes is located proximately with respect to the tissue of
interest and is designed to dispense the medication of interest
utilizing controlled electrical pulses. The pouch is connected with
the administering electrode of the electrode system via pumping
mechanism.
[0006] U.S. Pat. No. 5,733,259 to Valcke et al discloses a method
and apparatus for closed loop drug delivery. Specifically, a
closed-loop drug delivery system uses patient response and rule
based decision-making methods to achieve operator specified
responses for diagnostic purposes. In the preferred embodiment,
cardiac diagnosis is performed by pharmacologically stressing the
heart by administration of an exercise simulating agent drug. In
the preferred method, a protocol is defined, which preferably
includes a target for a physiologic variable, such as heart rate,
and a plan to achieve that target value. Preferably, the plan
includes a specification of the desired rate of increase in that
variable, such as the rate of increase in the heart rate per
minute. The plan comprises the desired changes in the physiologic
variable as a function of time.
[0007] U.S. Pat. No. 5,925,066 to Kroll et al discloses an atrial
arrhythmia sensor with drug and electrical therapy control
apparatus. The invention relates to an atrial arrhythmia sensor and
drug-dispensing apparatus is disclosed. The apparatus comprises a
multiphase, multistage intelligent system to monitor and treat
atrial fibrillation. The apparatus includes atrial rate sensing
means, cardiac pacing and antitachycardia pacing means, drug
delivery means including a self-cleaning catheter line with
multi-drug dispensing capability preferably operated using a dual
pump arrangement and an iontophoretic device. The drug delivery
system may also include a porous catheter to discharge drug into
the atrium. The intelligent system includes a memory implemented
logic (software) to continuously monitor the atrial rate and
initiate a response of either cardiac pacing, antitachycardia
pacing or drug dispensing based on preset cardiac activity
parameters. The system also includes a medical history-recording
feature.
[0008] U.S. Pat. No. 5,527,344 to Arzbaecher et al discloses a
pharmacological atrial defibrillator and method. In this invention,
a method and an implantable apparatus for automatically delivering
a defibrillating drug to a patient upon detection of the onset of
atrial fibrillation are disclosed. Atrial activity of a heart is
detected and monitored. A delivery time is continuously computed
and a delivery signal is emitted as a function of the monitored
level of the atrial activity. When the delivery signal is emitted,
an infusion pump discharges a defibrillating drug into the
bloodstream of the patient. The atrial activity is also
continuously monitored for computing a pacing time at which a
pacing signal is emitted as a second function of the monitored
level of atrial activity. When the pacing signal is emitted a pacer
paces the atrium of the heart.
[0009] U.S. Pat. No. 5,135,480 to Bannon et al discloses a
transdermal drug delivery device. More specifically, the invention
relates to a transdermal device having a detachably mounted
electrode with a first surface adapted for contact with human skin
and through which a drug substance contained in the electrode
passes to the skin under the influence of an iontophoretic or
electro-osmotic force and a second surface which is electrically
conducting, the electrode has a surface area in contact with the
skin, in use, in the range 0.1 to 30 cm and a drug dissolved or
dispersed in a hydrophilic medium at a concentration in the range
0.1 to 15% (w/v) based on the hydrophilic medium.
[0010] U.S. Pat. No. 6,091,989 to Swerdlow et al discloses a method
and apparatus for reduction of pain from electric shock therapies.
The invention discloses a method and apparatus for pretreating a
patient prior to a therapeutic painful stimulus, comprising the
application of pain inhibiting stimuli to a patient prior to an
application of the therapeutic painful stimulus. Applying
pain-inhibiting stimuli comprises the steps of sensing a need for
the therapeutic painful stimulus, preparing to deliver the pain
inhibiting stimuli to the patient prior to applying the therapeutic
painful stimulus, and delivering the pain inhibiting stimuli to the
patient prior to applying the therapeutic painful stimulus. The
method and apparatus are embodied in a fully automatic; fully
implantable, single or dual chamber atrial or ventricular
cardioverter-defibrillators. The pain inhibiting prepulse method is
intended primarily for use in conscious patients but may also be
used in sleeping patients.
[0011] As can be seen from the prior art recited hereinabove,
alleviation of cardioversion shock pain is an important
consideration in cardiac therapy. However, there is a need for a
closed loop controlled system to automatically deliver pain
analgesics and/or threshold reduction medications prior to or
contemporaneous with an atrial defibrillation shock or other drug
delivery therapy that may be associated with discomfort or
pain.
SUMMARY OF THE INVENTION
[0012] The present invention generally relates to a drug delivery
device in wireless communication with an implanted medical device
that preferably provides drugs transdermally prior to the delivery
of therapy by the implanted device. The system is preferably
telemetry or wireless communication-enabled to exchange data with
the implanted device to thereby identify preshock events so that
shock attenuation drugs could be delivered prior to an atrial
defibrillation shock. More specifically, an iontophoretic drug
delivery device is externally mounted on a patient's body, and is
interconnected by communication transmission channel with an
implanted medical device in the patient. The external device and
the implanted medical device are in a bi-directional data exchange
using telemetry and equivalent wireless communication systems
therebetween.
[0013] Further, the external iontophoretic drug delivery device and
the implanted medical device are independently accessible to a
programmer or an Independent Remote Monitor (IRM) external device
for interrogation and reprogramming of parameters as needed.
Furthermore, through either the IRM or a programmer, data may be
transmitted to a PC for review by physicians or caregivers.
Similarly, the data may be transferred to a server, which may be
accessible to a plurality of users of the data for analysis,
follow-up or research and development purposes.
[0014] Further, through media such as the Internet, intranet,
extranet or World Wide Web, data from the server may be accessible
by third parties, remotely to follow-up the patient and provide
recommendations for adjustment or therapy as needed.
[0015] One aspect of the invention relates to the provision of one
or more therapy regimens to the body, including two or more
discreet medical devices, at least one of which medical devices is
implanted into the living body and the other externally mounted,
and being in bi-directional data communication and exchange with
the implanted device.
[0016] Yet another aspect of the invention includes monitoring a
condition of a living body on a continuous basis to provide a shock
attenuation therapy before cardioversion electrical energy is
applied to at least one chamber of a patient's heart. Continuous
monitoring and communication between the external device and the
internal device coordinates the delivery of drug from the external
device before shock is delivered by the implatned medical device.
In this aspect of the invention, the external device and the
internal device communicate and identify preshock conditions that
indicate the eminence of cardioversion.
[0017] Yet another aspect of the invention includes a remote
communication system in which an external drug delivery device is
monitored and actuated to respond to indications of events that
would trigger therapy by an implanted medical device, which may
result in the perception of pain by the patient. The external
device may be remotely programmed to deliver drugs transdermally
immediately before or contemporaneous with the therapy. Similarly,
the communication system would allow a remote review and
programming of the implanted device. Further, amounts of pain
reducing drugs to be delivered may be remotely adjusted to
complement changes in cardioversion therapy.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 represents externally mounted drug delivery in
bi-directional communications with an implanted medical device.
[0019] FIG. 2 shows an external programmer or a remote home device
such as used to uplink and downlink data with both external drug
delivery device and the implanted medical device.
[0020] FIG. 3 represents one aspect of the remote communication and
monitoring system of the present invention.
[0021] FIG. 4 is a schematic block diagram of an automatic atrial
cardioverter and pain alleviating system of the present invention
employing the automatic remote delivery of pain alleviating drug
therapy.
[0022] FIG. 5 illustrates a representative drug delivery
device.
[0023] FIG. 6 depicts a drug delivery system schematic block
diagram.
[0024] FIG. 7 represents a high-level logic flow diagram of the
present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0025] FIG. 1 is an illustration of an implantable medical device,
for instance, IMD adapted for use to communicate with an externally
mounted drug delivery device. The IMD implanted in patient 10
includes IMD 12. In accordance with conventional practice in the
art, IMD 12 is housed within a hermetically sealed biologically
inert outer casing which may itself be conductive so as to serve as
an indifferent electrode in the IMD's pacing cardioversion/sensing
circuit. One or more pacemaker leads collectively identified with
reference number 14 are electrically coupled to IMD 10 in a
conventional manner and extend into the patient's heart 16 via vein
18. Disposed generally near the distal end of leads 14 are one or
more exposed conductive electrodes for receiving electrical cardiac
signals and/or for delivering electrical pacing and/or
cardioversion/defibrillati- on stimuli to heart 16. As will be
appreciated by those of ordinary skill in the art, leads 14 may be
implanted with its distal end situated in the atrium and/or
ventricle of heart 16.
[0026] Although the present invention will be described herein in
one embodiment, which includes an implanted medical device, those
of ordinary skill in the art having the benefit of the present
disclosure will appreciate that the present invention may be
practiced in connection with numerous other types of implantable
medical device systems. As to every element, it may be replaced by
any one of infinite equivalent alternatives, only some of which are
disclosed in this specification.
[0027] As depicted in FIG. 1, external drug delivery device 20 is
linked via telemetry transmission 21 to IMD 12.
[0028] FIG. 2 is a variation of FIG. 1 in which programmer 22 is
shown in communication with implanted medical device 12 and
external drug delivery system 20. Specifically, programming unit 22
is in telemetry or wireless communication with implanted medical
device 12 and external drug delivery device 20 via uplink and
downlink communication channels 23 and 23', respectively.
Programmer 22 described herein with reference to FIG. 2 is
disclosed in more detail in U.S. Pat. No. 5,345,362 issued to
Thomas J. Winkler entitled "Portable Computer Apparatus with
Articulating Display Panel" which patent is hereby incorporated
herein by reference in its entirety. Similarly, other remote
devices that enable programming of IMD 12 and drug delivery device
20 such as a home monitor disclosed in U.S. patent applications
Ser. Nos. 09/776,265 and 60/190,272 entitled "Information Remote
Monitor (IRM) Medical Device" and "Heart Failure Quick Look Summary
for Patient Management Systems" respectively, which are hereby
incorporated herein by reference in their entireties.
[0029] FIG. 3 is another embodiment of the present invention
wherein data is communicated using various medium to transfer
information from IMD 12 and drug delivery device 20 via programmer,
IRM or equivalent device 22. As discussed hereinabove data from IMD
12 and drug delivery device 20 is uplinked to device 22 from which
it may be directed to a PC 24 or server 26 using, for example, a
modem, an ISDN line, fiber optic, cable, infrared,
bluetooth-enabled or equivalent direct or wireless communication
systems. Server 26 is also accessible directly to qualified users
at station 28. Further, server 26 may be accessible via Internet 30
to remote users 32.
[0030] With this exemplary communication network, caregivers,
physicians and other qualified personnel may be able to access and
review or reprogram the operations of IMD 12 and drug delivery
device 20 remotely. For example, user 28 may use a LAN1 or other
secure lines to access server 26 from which either current or
stored data relating to the operation of IMD 12 and drug delivery
device 20 could be obtained for evaluation and adjustment, or
remote patient monitoring. Similarly, remote users at station 32
may be able to access operational and finctional data of IMD 12 and
drug delivery device 20 via Internet 30.
[0031] One of the significant aspects of the present invention is
the use of a transdernally operable drug delivery device 20. It is
similar to the electrotransport drug delivery system disclosed in
Design Patent No. 384,745 to Lattin et al. Further, a similar
device is disclosed in U.S. Pat. No. 5,995,869 to Cormier et al.
Additionally, electrotransport delivery device with voltage
boosting circuit is disclosed in U.S. Pat. No. 6,035,234 to Riddle
et al. And an electrotransport device and method of setting the
output using the same drug delivery device is disclosed in U.S.
Pat. No. 6,086,572 to Johnson et al. which patent applications are
incorporated herein by reference in their entireties.
[0032] The present invention implements a highly adaptable
communication link between the implanted device and the drug
delivery device disclosed in the prior art. The communication
system as indicated hereinabove without limitation could be
telemetry or as substantially described in U.S. Pat. No. 5,683,432
and 5,843,139, or an equivalent medical device communication system
such as the one disclosed in U.S. Pat. No. 4,987,897 to Funke which
patent is herein incorporated by reference in its entirety.
Accordingly, the present invention provides a closed-loop drug
delivery system that operates in data communications with an
implanted device to attenuate the impact of shock and other
discomfort resulting from IMD therapy.
[0033] Referring now to FIG. 4, a fully implantable atrial
cardioverter system 12 embodying the present invention in
association with a schematically illustrated human heart 16 in need
of atrial fibrillation monitoring and potential cardioversion of
the atria 216, 218 and an external programmer 22 are shown. The
atrial cardioverter system 12 is capable of the sequential
initiation of delivery of a pain alleviating analgesic at
therapeutic levels followed by delivery of atrial cardioversion
electrical energy pulses or shocks of sufficient amplitude and
duration to effectively cardiovert the heart 16 in atrial
fibrillation. The portions of the heart 16 illustrated in FIG. 4
are the right ventricle (RV) 212, the left ventricle 214, the right
atrium (RA) 216, the left atrium 218, the SVC 220, the CS 221
including the CS ostium or opening 224, the left ventricular free
wall 226 and the inferior vena cava 227.
[0034] The system 30 generally includes an enclosure 232, for
hermetically sealing the internal circuit elements, battery,
telemetry antenna, a bipolar RV lead 234, and a RA-CS lead 236. The
enclosure 232 and leads 234 and 236 are arranged to be implanted
beneath the skin of a patient so as to render the atrial
cardioverter system 30 fully implantable.
[0035] The RV lead 234 preferably comprises an endocardial bipolar
lead having electrodes 238 and 240 arranged for establishing
electrical contact with the right ventricle 212 of the heart 16.
The electrodes 238 and 240 permit bipolar sensing of ventricular
depolarizations or R-waves in the right ventricle 212. As
illustrated, the lead 234 is preferably fed through the SVC 220,
the right atrium 216, and then into the right ventricle 212 to
lodge the electrodes 238, 240 in the apex thereof as
illustrated.
[0036] The RA-CS lead 236 generally includes a tip or CS
cardioverting electrode 244 and a proximal ring or RA cardioverting
electrode 246 as shown in U.S. Pat. No. 5,165,403, for example. As
illustrated, the RA-CS lead 236 is flexible and arranged to be
passed down the superior vena cava 220, into the right atrium 216,
into the coronary sinus ostium 224. The CS electrode 244 is
advanced into the coronary sinus channel 221 of the heart near the
left side thereof so that the first or tip electrode 244 is within
the coronary sinus channel 221 either within the coronary sinus 222
adjacent the left ventricle 214 and beneath the left atrium 218 or
most preferably within the great cardiac vein 223 adjacent the left
ventricle 214 and beneath the left atrium 218. The electrodes 244
and 246 are spaced apart such that when the CS electrode 244 is
positioned as described above, the RA electrode 246 is in the right
atrium 216. The CS electrode 244 together with the RA electrode 246
provides bipolar sensing of heart activity in the atria 216 and
218.
[0037] The CS electrode 244 and the RA electrode 246 also provide
for the delivery of defibrillating electrical energy to the atria.
Because the CS electrode 244 is located beneath the left atrium 218
near the left ventricle 214 and the RA electrode 246 is within the
right atrium 216, the cardioverting electrical energy, when applied
between these electrodes will be substantially confined to the
atria 216 and 218 of the heart 16. As a result, the electrical
energy applied to the right ventricle 212 and left ventricle 214
when the atria are cardioverted or defibrillated will be minimized.
This greatly reduces the potential for ventricular fibrillation of
the heart to be induced as a result of the application of
cardioversion electrical energy of the atria of the heart.
[0038] Further electrode systems and cardioversion pathways have
been disclosed and are suitable for use in the practice of the
present invention. One such atrial cardioversion electrode system
is disclosed in the article "Safety and Feasibility of Transvenous
Cardioversion in Atrial Tachycardia", by Blanc et al., published in
Cardiac Pacing, edited by Gomez, Future Pub. Co., 1985, pp
1526-1529. This electrode system employs a single lead with
electrodes located in the right atrium and in the pulmonary artery.
Delivery of atrial cardioversion shocks between an RV electrode and
a subcutaneous electrode is disclosed in U.S. Pat. No. 5,292,338.
Delivery of atrial defibrillation pulses between a coronary sinus
electrode and a subcutaneous electrode is also disclosed in U.S.
Pat. No. 5,314,430.
[0039] A further suitable atrial cardioversion electrode system is
disclosed in U.S. Pat. No. 5,549,642 incorporated herein by
reference in its entirety. The electrode system disclosed therein
includes an RA/SVC electrode (alone or optionally coupled to a
subcutaneous electrode) and a CS electrode. The elongated RA/SVC
electrode appears to provide atrial defibrillation thresholds in
the range of about 1.0 Joule or less across a substantial portion
of the patient population which represents a substantial
improvement over the RA or SVC to CS/great vein electrode system
employed in the above-referenced '403 patent.
[0040] Any of the above atrial cardioversion electrode systems and
associated atrial and/or ventricular leads may be used in the
practice of the present invention. However, even an approximately
1.0 joule cardioversion shock can be painful to a substantial
portion of the population, particularly since atrial fibrillation
episodes repeat frequently, requiring frequent cardioversion.
[0041] Within the enclosure 232, the system 30 includes a
ventricular sense amplifier 250 coupled to the RV lead 234 to
receive electrical signals in the ventricle across the bipolar
electrode pair 238, 240 and an R-wave detector 252 to detect the
R-waves therefrom. The ventricular sense amplifier 250 and the
R-wave detector 252 form a first detecting means that senses
R-waves in the electrogram transmitted to ventricular sense
amplifier by the RV lead 234. The R-wave detector 252 is of the
type well known in the art, which provides an output pulse upon the
occurrence of an R-wave being sensed during a cardiac cycle of the
heart. The delivery of the atrial defibrillation shock or pulse is
timed from the R-wave employing the ventricular timer 264 as
described below.
[0042] The lead and electrode systems in certain embodiments of the
above-referenced '338, '403 and '430 and '642 patents include an RV
defibrillation electrode positioned on an RV lead inserted into the
right ventricle and a pair of ventricular sense electrodes.
Alternatively, in the atrial cardioversion system depicted in FIG.
4, common ventricular pacing leads having bipolar screw-in
ventricular electrodes of this type may be employed as pace/sense
electrodes 238, 240.
[0043] An atrial sense amplifier 254 is coupled to the RA-CS lead
236 to receive electrical signals or P-waves across the right
atrium 216. The atrial sense amplifier 254 forms a second detecting
means for detecting P-wave atrial activity of the heart picked up
by the CS electrode 244 and RA electrode 246 of the RA-CS lead 236.
The P-wave output signal of the atrial sense amplifier 254 is
coupled to an analog to digital converter 260 which converts the
analog signal representative of the atrial activity of the heart to
digital samples for further processing to determine if atrial
fibrillation is present and if the atrial cardioversion shock is
effective in converting the atria to a normal atrial rate.
[0044] The enclosure 232 of the atrial cardioverter system 30
further include a microcomputer 262 that is preferably implemented
in a manner disclosed in the above-referenced '338 patent and
further as described hereinafter with respect to the flow diagram
of FIG. 7. The implementation of the microcomputer 262 in
accordance with this embodiment of the present invention results in
a plurality of functional stages and RAM/ROM 282 for storing
operating algorithms and programmable parameters as well as
accumulated operating data for subsequent telemetry out to the
external programmer 22.
[0045] The circuitry includes the ventricular timer 264 for timing
various intervals that recur in each QRST cycle as well as the
R-wave synchronization time interval, an interval set stage 266 for
selecting time intervals to be timed out in the ventricular timer
264, a delay timer 265 for timing out further delay times set in
interval set stage 266 for the delivery of the pain alleviating
therapy, an optional patient warning device 267 and warning set
register 263, a cardioversion energy level set stage 269, an atrial
fibrillation detector 270, a charge delivery control stage 272, an
analgesic delivery control stage 290, and a computation stage
280.
[0046] The microcomputer 262 is arranged to operate in conjunction
with RAM/ROM memory 282 which may be coupled to the microcomputer
262 by a multi-bit address bus and a bi-directional multiple-bit
data bus. This permits the microcomputer 262 to address desired
memory locations within the memory for executing write or read
operations. During a write operation, the microcomputer 262 stores
data, such as time intervals or operating parameters in the memory
282 at the addresses defined by multiple-bit data bus. During a
read operation, the microcomputer 262 obtains data from the memory
at the storage locations identified by the multiple-bit addresses
provided over the address bus and receives the data from the memory
282 over the bi-directional data bus. Data related to the
detections of atrial fibrillation and the deliveries of the
therapies may be recorded in the RAM memory 282 for interrogation
and telemetry out to the external programmer 22 in a manner well
known in the art.
[0047] Detection of atrial fibrillation may be accomplished in
atrial fibrillation detector 270, in conjunction with computation
stage 280, of microcomputer 262 from the digitized P-waves detected
by atrial sense amplifier 254 using any of the various atrial
fibrillation detection methodologies known to the art. Generally,
atrial fibrillation may be detected in response to an extended
series of high rate (e.g. 240 BPM or greater) atrial
depolarizations or P-waves. If greater specificity for atrial
fibrillation is desired, analysis of regularity of rate waveform
morphology may also be employed.
[0048] Termination of atrial fibrillation may be detected in
response to a decrease in the rate of atrial depolarizations and/or
an increase in their regularity.
[0049] Appropriate detection methodologies are disclosed in the
article "Automatic Tachycardia Recognition", by Arzbaecher et al.,
published in PACE, Vol. 7, May-June 1984, part II, pages 541-547
and in PCT Application No. US92/02829, Publication No. WO 92/18198
by Adams et al., both incorporated herein by reference in their
entireties. In the PCT application, careful synchronization of the
high voltage atrial defibrillation pulse to the ventricles to avoid
induction of ventricular tachycardia or fibrillation is also
discussed.
[0050] In addition, in the context of devices which automatically
detect the occurrence of atrial fibrillation, the patient may
optionally be warned of the detection of atrial fibrillation to be
ready for the delivery of the atrial cardioversion shock through
operation of the warning device 267. In this alternate variation of
the embodiment of the invention, a warning may be provided to the
patient of the diagnosis of atrial fibrillation and the
commencement of delivery of the pain alleviation drug therapy. The
warning may be effected in the manner described in U.S. Pat. No.
5,332,400 incorporated herein by reference in its entirety, but is
preferably effected by energizing a piezoelectric crystal
oscillator that oscillates at an audible frequency intense enough
for the patient to hear it and take precautions, if necessary. The
patient may also optionally be provided with a limited function
programmer 22 for use in communicating a command to the
microcomputer 262 to prevent delivery of the cardioversion shock
until the patient feels the effects of the pain alleviation
therapy, at which time the patient may employ the programmer 22 to
enable delivery of the cardioversion shock, subject to
re-verification of the presence of the atrial fibrillation.
[0051] In this regard, the system 30 also includes the warning set
register 263, the delay timer 265, and the warning device 267 that
are utilized for generating the warning alarm for the patient when
the atrial fibrillation detector 270 determines that the atria are
in fibrillation. The warning device 267 may constitute an audible
alarm sounding piezoelectric crystal oscillator for warning the
patient that atrial fibrillation has been detected and that
cardioverting electrical energy will be applied to the patient's
atria.
[0052] If a programmer 22 is provided, it may also optionally
include a patient activated command signal to initiate the delivery
of the pain alleviating and cardioversion therapies in response to
symptomatic atrial fibrillation. In this context as well, the
ability to use the programmer 22 to delay the delivery of the
cardioversion pulse until the patient has felt the effects of the
pain alleviating therapy is believed valuable.
[0053] After the fibrillation detection warning is delivered to the
patient, or after the patient requests cardioversion therapy by
means of the programmer 22, register 263 is set to indicate that
the patient has received the fibrillation detection warning or has
requested therapy. Immediately thereafter, the delay timer 265
starts timing the warning delay period and initiates communication
to drug delivery system 20 via RF transmitter 292 and antenna 294.
The delay period defines a time interval from when the patient
receives the warning or requests therapy to when the patient should
first expect to receive the cardioverting electrical energy. The
delay time is preferably programmable between one minute and twenty
minutes to afford sufficient time to permit the pain alleviating
therapy to take effect and for the patient to prepare for receiving
the atrial cardioverting electrical energy. A second warning may
optionally be given slightly before delivery of the cardioversion
pulse, if desired. If the patient does not perceive the analgesic
effect of the pain alleviating therapy during the warning delay,
the patient may use the programmer 22 to reset the delay timer 265
to delay delivery of the cardioversion pulse until timer 265
expires. Alternatively, the programmer may instead allow the
patient to delay delivery of the pulse until the patient perceives
the analgesic effect, and allow delivery of the cardioversion
therapy only following a patient initiated enable signal to the
implanted device indicating that therapy may be delivered. As yet
another alternative, the programmer may be employed to simply abort
the therapy during the warning delay, which may be especially
useful if therapy was initially requested by the patient, and the
patient's symptoms have subsided.
[0054] A warning system as described above, including apparatus
specifically dedicated to providing the warning may not be
necessary if the patient can independently feel the analgesic take
effect.
[0055] FIG. 5 illustrates a representative electrotransport
delivery device that may be used in conjunction with the present
invention. Device 20 comprises an upper housing 46, a circuit board
assembly 48, a lower housing 56, anode electrode 57, cathode
electrode 59, anode reservoir 62, cathode reservoir 64 and
skin-compatible adhesive 67. Upper housing 46 has lateral wings 45,
which assist in holding device 20 on a patient's skin. Upper
housing 46 is preferably composed of an injection moldable
elastomer (e.g., ethylene vinyl acetate). Printed circuit board
assembly 48 comprises an integrated circuit 49 coupled to discrete
components 52, antenna 54 and battery 50. Circuit board assembly 48
is attached to housing 46 by posts (not shown in FIG. 5) passing
through openings 43a and 43b, the ends of the posts being
heated/melted in order to heat stake the circuit board assembly 48
to the housing 46. Lower housing 56 is attached to the upper
housing 46 by means of adhesive 67, the upper surface 72 of
adhesive 67 beings adhered to both lower housing 56 and upper
housing 46 including the bottom surfaces of wings 45.
[0056] Shown (partially) on the underside of circuit board assembly
48 is a button cell battery 50. Other types of batteries may also
be employed to power device 20.
[0057] The device 20 is generally comprised of battery 50,
electronic circuitry 49, 52, 54, electrodes 57, 59, and hydrogel
drug reservoirs 62, 64, all of which are integrated into a
self-contained unit. The outputs (not shown in FIG. 5) of the
circuit board assembly 48 make electrical contact with the
electrodes 59, and 57 through openings 58, 58' in the depressions
60, 60' formed in lower housing 56, by means of electrically
conductive adhesive strips 66, 66'. Electrodes 57 and 59, in turn,
are in direct mechanical and electrical contact with the top sides
68, 68' of drug reservoirs 62 and 64. The bottom sides 70', 70 of
drug reservoirs 62, 64 contact the patient's skin through the
openings 65', 65 in adhesive 67.
[0058] Device 20 optionally has a feature, which allows the patient
to self-administer a dose of drug by electrotransport. Upon
depression of push button switch 42, the electronic circuitry on
circuit board assembly 48 delivers a predetermined DC current to
the electrode/reservoirs 57, 62 and 59, 64 for a delivery interval
of predetermined length. The push button switch 42 is conveniently
located on the top side of device 20 and is easily actuated through
clothing. A double press of the push button switch 42 within a
short time period, e.g., three seconds, is preferably used to
activate the device for delivery of drug, thereby minimizing the
likelihood of inadvertent activation of the device 20. Preferably,
the device transmits to the user a visual, tactile and/or audible
confirmation of the onset of the drug delivery interval by means of
LED 44 becoming lit, TENs-like stimulation via electrodes 57 and 59
and/or an audible sound signal from, e.g., a "beeper". Drug is
delivered through the patient's skin by electrotransport, e.g., on
the arm or body, over the predetermined delivery interval.
[0059] Anodic electrode 57 is preferably comprised of silver and
cathodic electrode 59 is preferably comprised of silver chloride.
Both reservoirs 62 and 64 are preferably comprised of polymeric gel
materials. Electrodes 57, 59 and reservoirs 62, 64 are retained by
lower housing 56.
[0060] A liquid drug solution or suspension is contained in at
least one of the reservoirs 62 and 64. Drug concentrations in the
range of approximately 1.times.10.sup.-4 M to 1.0 M or more can be
used, with drug concentrations, in the lower portion of the range
being preferred. Typically, the reservoir containing the drug will
also contain the selected countersensitizing agent, in an amount
and concentration effective to provide the flux necessary to reduce
or prevent sensitization of the skin or mucosa.
[0061] FIG. 6 shows a simplified schematic block diagram of drug
delivery system 20 integrated circuit 49. Microprocessor 72 under
control of a program contained in RAM/ROM 74 (interconnected via
bi-directional bus 79) receives commands from IMD 12 through
receiver 78 and antenna 54. Upon a command to initiate drug
delivery, the microprocessor 72 initiates drug delivery through
drug delivery control block 80, which initiates iontophoretic drug
delivery through two electrodes (not shown). Timer 77 times the
length of time for drug delivery under control of intervals stored
in RAM/ROM 74 previously programmed via programmer 22 (not shown in
FIG. 6). Upon timer 77 time out, a signal is sent to IMD 12 from
transmitter block 76 and antenna 54 using the same telemetry system
described herein above.
[0062] The infusion of various analgesic drugs or agents (or,
simply "analgesics") including opiates (i.e. morphine sulfate,
hydromorphone) and non-opiates (i.e. alpha-2 adrenergic agonists
and neuron specific calcium channel blocking agents) have
demonstrated rapid and effective analgesia following
administration. Dependent upon the specific analgesic administered,
it is also reported that the onset of pain suppression occurs in a
couple of minutes to one hour, and the duration of analgesia may
range from 4-24 hours. The delay in analgesia onset is not
problematic, since rapid cardioversion is not necessary for atrial
fibrillation as opposed to ventricular fibrillation. Time to
analgesia can be utilized by the system 30 to re-verify the
continuation of atrial fibrillation, charge storage capacitors to
deliver the cardioversion shock, and ensure ventricular sensing to
allow cardioversion shock synchronization with the R-wave of the
cardiac cycle.
[0063] A first alternative embodiment of the invention may employ
the drug delivery system 20 for delivery of a cardioversion or
defibrillation threshold reducing agent such as D-salotol,
Procainamide or Quinidine as an alternative to, or in conjunction
with, delivery of the pain alleviating therapy discussed above. The
reduction of defibrillation threshold in such case would provide
the possibility of a reduced amplitude, less painful cardioversion
pulse. The delivery of a threshold reducing agent thus can be
employed as a pain alleviating therapy or as part of a pain
alleviating therapy. In a more complex embodiment, two separate
drug delivery systems might be employed to allow delivery of the
threshold reducing agent alone or in conjunction with an
analgesic.
[0064] A second alternative embodiment of the invention may employ
the drug delivery system 20 for delivery of diuretic and blood
pressure regulating agents such as Thiazide diuretics
(hydrochlorothiazide, chlorthalidone), usually adequate for mild
heart failure, loop diuretics (furosemide, bumetanide, ethacrynic
acid) reserved for severe volume overload or thiazide-resistant
edema. Additionally, ACE inhibitors have been shown to prevent or
slow the progression of heart failure in patients with symptomatic
and asymptomatic left ventricular dysfunction. Currently, four
agents are used for the treatment of CHF (Congestive Heart
Failure): captopril, enalapril, lisinopril, and quinapril. The
implementation of IMD 12 of this embodiment would use the Medtronic
Chronicle.TM. CHF monitoring system such as described in U.S. Pat.
Nos. 5,535,752 and 6,155,267, incorporated herein by reference in
their entireties. The IMD 12, as described in the '267 patent,
would monitor chronic data representative of at least one
physiological parameter. The chronic data is monitored to detect
changes in state of the at least one physiological parameter. Data
associated with detected changes in state is stored within IMD 12.
The detection of changes in state of the at least one physiological
parameter is performed by establishing a baseline (e.g., a center
reference line and upper and lower control limits), and then
determining if the chronic data being monitored satisfies
predetermined, preprogrammed conditions (e.g., conditions based on
the center reference line and the upper and lower control limits)
indicative of a change in state of the at least one physiological
parameter. If data occurs outside of these predetermined limits,
the IMD 12 sends telemetry signals to drug delivery system 20 to
initiate the delivery of the appropriate drug as described herein
above.
[0065] A third alternative embodiment may utilize the drug delivery
system 20 as the patient activator/programmer 22 by incorporating
the features and function as described in U.S. Pat. No. 5,987,356
incorporated herein by reference in its entirety.
[0066] FIG. 7 depicts a flow chart of an operation of the system
shown in FIG. 4 in accordance with the present invention. At step
S100, which continues at all times (except during the delivery of
atrial cardioversion shock), atrial activity of the heart is
sensed. At step 102, the atrial fibrillation detection algorithm is
invoked in atrial fibrillation detector 270. If it is detected,
then in step S104, the IMD 30 transmits a signal to the drug
delivery system 20 via drug delivery control 290, RF transmitter
292 and antenna 294.to initiate delivery at S105 of a programmed
bolus of the pain alleviating drug from drug dispenser 20.
[0067] The charge delivery control 272 may be commanded to start
charge up of the charge storage capacitors, but it is preferred to
delay capacitor charge up until the end of the delay for the
analgesic to take effect and commence capacitor charge up during
the analgesic time course, that is, the time period that the
analgesia effect is expected to continue. At S107 the drug delivery
device 20 transmits a confirmation of drug delivery completion back
to the IMD 12. Optional warning steps for the patients to show the
status of the detection, drug delivery and cardioverter status may
be included but are not shown in the flow chart of FIG. 7.
[0068] A delay timer 265 is loaded and enabled to time out the
delay for the analgesia effect to take place in steps S106 and
S108. During this delay, the continuation of the atrial
fibrillation episode may be verified in steps S100 and S102 and the
algorithm may optionally be halted at that point. However, since
atrial fibrillation bouts reoccur and since the bolus of pain
alleviating drug is already delivered, reconfirmation at the end of
the delay times is sufficient to determine whether or not to
deliver the cardioversion shock therapy.
[0069] When the delay timer 265 times out in step S108, the delay
timer 265 is reset for the analgesic time course and is started in
step S110. The atrial fibrillation detection is re-verified in step
S112 during the analgesic time course. If it only re-verified after
the analgesic time course times out, then it is necessary to repeat
steps S104-S114 until it is re-verified during an analgesic time
course.
[0070] Then, in step S116, a charge delivery control 272 is
commanded to enable the storage capacitor charge circuit 274 to
charge the high voltage output capacitors up to the cardioversion
energy set in level stage 269. The microcomputer 262 then sets a
synchronization time interval in interval set stage 266 from an
R-wave detected by R-wave detector 252. The ventricular timer 264
then provides a blanking signal to the ventricular and atrial sense
amplifiers 250 and 254. Both operations may be performed in step S
118. Re-verification of continued atrial fibrillation may also be
performed between steps S116 and S118.
[0071] At the expiration of the synchronization time interval in
ventricular timer 264, a command is applied through the charge
delivery control to operate a discharge circuit 276 to discharge
the atrial cardioversion shock via electrodes 244 and 246. After
the atrial cardioversion shock is delivered, the atrial and
ventricular sense amplifiers are again enabled, and the presence or
absence of atrial fibrillation is again tested in step S112. If the
episode is terminated, then the algorithm loops back to step
S100.
[0072] If the episode is not terminated, the steps of FIG. 7 may be
repeated. After a certain number of attempts, the available
therapies may be exhausted. Whether or not the therapies are
successful, the patient will likely have been advised to contact
the attending physician. The event history of the episodes and
delivered therapies are recorded in RAM 282 for subsequent
telemetry out and analysis by the physician in a manner well known
in the art in order to assist in reprogramming therapies.
[0073] Thus, the methodological sequence to provide the pain
alleviating therapy to counter the pain induced by delivery of
atrial cardioversion energy includes the initial detection of
atrial fibrillation, optional warning to the patient, drug infusion
therapy to produce analgesia, time out to allow analgesia to take
effect and the charge storage capacitors to be charged,
reverification of atrial fibrillation, delivery of the
cardioversion energy, and verification that successful atrial
defibrillation has taken place. Should successful atrial
cardioversion not take place, the steps of FIG. 7, would be
reinitiated, except that analgesic drug delivery would not be
repeated unless the analgesic time course time had timed out in
order to prevent drug overdose.
[0074] Depending on the analgesic employed, it may also be
desirable to include a further timer to inhibit delivery of a
further analgesic bolus timed from the previous delivery for a
further time delay to prevent drug overdose. Such a timer may take
into account the cumulative amount of analgesic delivered over a
set time period.
[0075] In addition, it may be desireable to provide the patient
with the option of using programmer 22 to temporarily program the
delivery of an increased quantity of analgesic, if the desired
analgesia effect is not achieved at the permanently programmed
setting. A time and date record of such patient programmed
increases may be kept in the system memory for review by the
physician, and the repetitive use of the programmer may be
inhibited.
[0076] The preceding specific embodiments are illustrative of the
practice of the invention. It is to be understood, therefore, that
other expedients known to those of skill in the art or disclosed
herein may be employed without reporting from the invention or the
scope of the appended claim. It is therefore to be understood
within the scope of the appended claims; the invention may be
practiced otherwise than is specifically described, without
departing from the scope of the present invention.
* * * * *