Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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1"APPARA'rUS, CATHETER AND MæTHOD FOR CHEMICAL coNTA~r
DISSO WTION OF GALLSTONES
~his application is a continuation-in-part of copending
5application Serial No. 07/180,099 filed April 11, 1988 which
` 6 was a continuation~in-part of application Serial No.
7 06/871,775, filed June 9, 1986.
8 BACKGROVND OF THE INV~NTION
g For most individuals who s~lffer from gallstones, the
1~ treatment of choice is to have a cholecystectomy, or surgical
11 removal of the gallbladder. Each year 500,000 such operations
12 are done in the United States alone. Recently, because of the
13 cost, prolonged recuperation time and possible side ef~ects
14 associated with this sùrqery, methods have been developed for
chemicall~ removin~ gallstones ~L_~ib~ Generally, this
proce-lure involves inserting a catheter into the gallbladder
17 followe~ by infusing a chemical solvent capable of dissolving
18i the gallstone. The procedtlre thus a~oids the need for and
19 attendant risk of surgery.
A variety of chemical solvents have been tried and found
i 21 to exhibit varying efficiencies of gallstone dissolution,
22 depending on the chemical nature of the ~allstone. Gallstones
~! 23 are generally composed of cholesterol or calcium salts,
24 partic~larly calcium bilirubinate and calcium carbonate.
Lipi~ solvents are effective at dissolving cholesterol
26 gallstones, whereas these solvents have little or no
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27 solubilizing e~fect on gallstones composed of calcium salts.
28 Thus, ~iethyl ether readily dissolves cholesterol gallstones,
29 àn~ ~ther solvents such as mono-octanoin, and octadiol
3~ (glyc~ry1-1-octyl ether) also have good solubili~ing
31 properties. Unfortunately, few if any solvents are
32 satisfactory for dissolving calcium gallstones~ The inven-tion
33 here.in will therefore find princ.ipal utility in cholesterol
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1 ~all~tone removal. It has been recognized that ether
2 compounds such as diethylether have excellent cholesterol
3 solubilizing properties, low viscosity and very good kine~ic
4 solubility but diethylether is hazardous since it boils below
body temperature. Recently methyl tert-butyl ether (MTBE),
6 a solv~nt hithertofore used prlmarily a5 a gasoline additive
7 and a chromatographic 501vent ~nedia, has been used for
8 gallstone dissolution since it exhibits all the properties of
g ethers. Moreover, MTBE boils above body temperature and the
solvent rapidly dissolves the galls~ones without damaging the
11 mucosa of the gallbladder.
12 The ef fectiveness of such new solvents has led to
13 considerable activity focused on developing apparatus and
14 methods for delivering MTBE and similar solvents to patients
suffering from gallstones in ways to most rapidly and
16 effectively solub~ lize gallstones wlthout the complications
17 arising from introducing such solvents into ~he body. (For
18 brevity herein, the description will be wit~ resp~ct to use
19 of the MTBE as a solvent. Xt will ~e recognized, however,
that this invention will be applicable to a number of
21 different sol~ents).
22 Physicians currently tr~at cholestierol ~allstones by
23 infusing MTBE into the gallbl~dder throush a percutaneously
24 positioned catheter thro~gh which ~TBE ls manually passed
using glass syring~s [Walker, L~ncet, ~ 874 (1891);
26 Shortsleeve, RadioloqY, 153, 547 (1984); and Teplick,
27 Radioloqy~ 379 ~1984)]. Additionally, phy~icians have
28 available fixed volume syringe pumps, such as described in
29 U.S. Patent No. 4,655,7~4 to ~histle et al. to infuse and
aspirate MTBE. There are several complications associated
~1 with either the manual infusion or the fixed volumP pump-
32 assisted i~fusion procedure.
33 When MTBE is delivered manually via glass syringes or
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1 with the aid of a fixed volume-cycle pump, spontaneous
2 gallbladder contraction or over filliny of the gallbladder
3 cannot be detected or controlled. Consequently, MTBE
4 periodically empties into the duodenum, producing duodenal
mucosal injury, which in turn produces nausea, vomiting,
6 duodenal erosions and ac ompanying pain of suf f icient
7 intensity to necessitate ~requen~ administration o~
8 analgesics. In addition, when ill ~he duodenum, MTBE can be
9 absorbed in~o the blood stream, which in turn may result ln
somnolence or hemolysis and concomitantly the presence of the
11 intense and irritating MTBE odor in the patien~'s ~reath.
12 Other proble~s associated with the manual or pump
13 associated syringe method involve inefficient removal of
14 insoluble gallstone particles which constitute varying
percentages of cholesterol gallstones. Such particle~ are
16 often left behind in the g~llbladder, after MTBE dissolves the
17 cholesterol portion, in procedures involving syringes or
18 syringe pumps. These particle~ often 6erve as the nidus for
19 new gallstone formation~ Addit~on~lly, both procedures are
time consuming, laborious and require individual~ that are
21 highly skilled in their use. Consequently, the procedures are
22 expensive because of the attendant costs associated wit~
23 having a highly skilled staff of professional people to
24 perform the procedure for prolonged ti~s, often 12 hours or
more. In addition, a fixed volume syringe pump can not ,
26 prevent bile from entering the gallbladder during the course
27 of its secretion by the liver. Bile in the gallbladder
28 impedes the solvent's contact with stones and henca delays the
29 proceC~ sf dissolutisn
It is obvious that delivering MTBE to a patient requires
.
31 the utmost care to avoid releasing the solvent into the
32 patient's bodily fluids or outside the area o~ treatment.
- 33 Thus a key consideration in developiAy devices used in the
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l chemic~l therapy of gallstone dissolution ls ensuring the
2 contr~lled delivery and removal of the solvent used to
3 dissolve the gallstones. Considering that studies have shown
4 that solvents such as MT~E are injuriou~iif they pass into the
intestine where they get absorbed, there is a critical need
6 for devices that ensure tihat ;such chemicals will not be
7 released during chemic~l therapy for gall~itone remov~l. At
8 the same time ~uch devices must be able to maintain high
g solvent circulation rates into the gallbladder to create the
necessar~ tur~ulence that will enhance dis~olution and aid in
ll evacuating the insoluble residue.
12 Also, because of the need to ensure containment of
13 solvents, in addition to the sa~ety features described ~bove,
14 a sultable devloe should be "user friendly" ~nd not require
the presence of highly skilled technicians to run the device.
16 Further, for the same reasons, it sho~ld be easily
17 maintainable.
18 With a little reflection, it becom2s apparent that ther~
19 are considerable hurdles to surmount if on~ is to develop a
devioe that has the features descrlbed above~ ~or instance,
21 it must be 1'intelligent" and capable of sensing instantaneou~i
22 changes in gallbladder pressure brought about by ~allbladd~r
23 contractions or by infusing the solvent, and rapidly relay
24 this information to controlling feedback circuits. This is
a crucial feature for suc~ a devic~. If a gallstone should
26 in some way prevent the necessary circulation of the solvent
27 throuqh the gallbladder, a crltical pressure will build up,
28 possihly rupturing the organ or causing leakage of the solvent
29 from the gallbladder through the cystic duct into the common
duct and intestine. Thus the device must be "intelligent" in
31 the sense that i~ senses gall~ladder pressure changes over a
32 predefined range and reacts ~ast enough to keep the pressure
33 in that range, shutting down or reacting appropriately if ~he ~;
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1 pressure persists outside the range. Moreover, it would be
2 desil-able to have a device that not only is capable ~f
3 shuttinc! down, but actually can flush out any debris causing
4 the ~lockage, and resume normal operation should the dehris
be removedO Such device shoulcl prevent intra-gallbladder
6 pressure from rising above leak~ge llmit and from falling
7 below the pressure under which b.~le will be sucked in~co the
8 gallbladder from the biliary duct..
5-~MAR/ OF rHE INVENTION
11 The invention herein comprises an apparatus and a method
12 for its use wh~ch are for therapeutic treatment of obstruc-
13 tions in bodily organs by high rate solvent circulation,
14 particularly for gallbladder or co~mon bile duck stones. The
lS apparatus has the desirable feature of continuous high rate
16 infusion and aspiratlon while prevent-ing solvent leakage from
17 the bodily organ being tre~ted. The apparatus comprises a
18 forward or reverse acting solvent delivery means that is
19 linked via a pressure transducer to a feedback controller
circuit.
21 The apparatus is preset to perfuse within a set pressure
Z2 range. Continuous feed~ack of true intraluminal organ
23 pressure to a contrQller circult ~ia the t.ransducer controls
24 the rate and the net direction of solvent delivery by the
apparatus ~nd is determinative of whether the apparatus acts
26 in the forward or reverse mode. Over this range the solven~
27 is constantly passed from a reservoir into the gallbladd~r,
28 and from the gallbladd r it is aspirate~ to a suitable
29 receptacle. D~livery and removal of khe solvent is at a rate
sufficient to effect gallstone dissolution and fra~mentation,
31 agitation and aspiration of insoluble fraginents. Should there
32 : be an increase :in pressure, a feedback loop switches the
33 d~vice into a high pre~sure mode, thereby diverting the
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1 solvent away from the gallbladder. If after a predetermined
2 perio~ of time the pressure sensing transducer readings from
3 the gallbladder indicate a return to normal operating pressure
4 range, the device automatically reinitiates the normal
infusion and aspiration (perfusion) mode.
6 An additional feature o the invention is a self purging
7 mechanism. After a preset interv2l1, if the pressure does not
~ decrease, the device enPers a reverse mode to purge the
9 aspiration port of the catheter, whereby 1uid is aspirated
lo backward through the infusion port and infused through the
11 aspiration port to purge Por discrete short intervals, duriny
12 which time the pressure ~n the organ is continuously
13 monitored. Once the blockage is removed by this "self
14 purging" action, the pressure transducer again indicatss
normal operating pressure, and the devlce resumes actlon 1n
16 the normal pressure ~ode. However, should the obstruction not
17 be removable after a predetermined number of purge cycles, an
18 alarm circuit is activated, so notifying the us~r. A further
19 feature of the invention is that it i8 able to distinguish
clinically significant pressure changes occurring wi~hin the
21 gallbladder which leads to emptying o~ gallbladder contents
22 into the duodenum from those clinically in~ignificant chanqes
23 arising as a result of coughing, laughing or like behavior.
24 This feature prevents needless changes or operating modes.
A further aspect of the invention is a catheter for the
26 contact dissolu~ion of gallstones having a solven~ infusion
27 lumen and a solvent aspiration lumen in side-by-side
28 relationship~ The catheter is sized for introduction of its
29 distal. portion into the gallbladder from outside the body.
Each lumen has at least one opening in the distal portion ~or
31 c~mmunication between th~ gallbladder and a remotely located
3~ pump. A third lumen provides a means to continuously sense
33 intra-gallbladder fluid pressure and to transmit an indication
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1 thereef to the controller, for con~rol of infusion and
aspiration of solvents via the lumens. An aspect of the
3 invention is that the cross-sectional area of the aspiration
4 lumen is larger than the cross-sectional area of the infusion
lumen. Fluid moves into and out of each lumen by a series of
6 openings in the walls of the catheter. The cross-sectional
7 area of each opening is less than the cross-sectional area o
8 the lumen with which the opening is in communication. Thie
9 catheter further includes a retention means to prevent the
catheter from being dislodged from the gallbladder. The
11 retention means is a curved formation of the distal portion
12 of the cat~eter. The pressure sensing means is located to lie
13 at the inner radius o~ the curved formation to prevent its
14 blockage by the mucosa of the gallbladder. Alternatively, the
retention means may be an inflatable balloon located adjacent
16 to the distal portion.
17 A tension string for holding the distal portion of the
18 ca~heter in a curved configuration is included. The catheter
19 also has a string passagc lumen in which the string is
located. Alternatively, the strin~ may bi~ located in eithex
21 the aspiration lumen, the infusion lumen or the pressure
22 sensing lumen.
23 The opening at the distal,end of the catheter is in
24 communication with the aspiration lumen. The catheter has ~t
least one aspiration opening, in the wall of the catheter in
26 communication with the aspiration lumen, which is located
27 proximal to all infusion openings. The proximally-located
28 aspiration opening is located adjacent to the point of entry
29 of th~ catheter into the gallbladder when the catheter ls in
position for operation.
31 The lumen and aspiration opening at the c~istal end of the
32 lumen are constructed and arranged to enable the catheter to
33 pass over a guide wixe. The catheter is made of material, for
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1 exam~l~ polyurethane, which is resistent to the solvent to be2 infu~e~ into said gallbladder.
The means for sensing the pressure of fluid within the
4 gallbladder includes a third fluid pressure transmitting lumen
extending ~ide by side with the infusion and aspiration lumens
6 and having a distal opening in the di~tal portion of the
7 catheter. The lumen is constructed to communicate intra-
8 gallbladder pressure to a remotely located pressuro transducer
9 via a hydrostatic 1uid column. The means for ~en~ing the
pressure of fluid within the third lumen comprises ~ pres.sure
11 transducer located at the proximal portion of the catheter.
12 Alternati~aly, the pressure transduc~r may be located at ~he
13 distal end of the catheter and provide in situ. gallbladder
14 pressure measurements. Such transducers for in situ use can
be piezoelectric, or ~iberoptic, and may be removably inserted
16 in a lumen of the catheter. The wlre~ or fiber of an in situ
17 transducer located at the distal end of the catheter can pass
18 through the pres~ure lumen, infusion lumen, or aspiraSlon
19 lumen or may be embedded into khe catheter's wall. The
catheter has a structural formation at it~ proximal end that
21 permits it to be ~sed only with a solvent deltvery system
22 ha~ing a predetermined mating structural formation that
23 prevents inadvertent use with non-mating sys~ems.
24 Alternatlvely the catheter has an ele~trical or fi~eroptic
connection at its proximal end th~t permits it to be used only
26 with 3 solvent delivery system having a predetermined
27 electrical or fiberoptic connection.
28 One aspect of the invent.ion is a microprocessor
29 programmed to execute an algorithm in response to an input
pressure signal derived from the yallbladder through a
31 pressure deter~ining module; a pump control module, to control
32 the speed and direction of an infusion pump pumping solvent
33 through an infusion lumen into the gallbladd~r of the patient
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1 and an aspiration pump pumping solvent through an aspiration
lumen out of the gallbladder of the patienti and a response
3 determination module to control the functions of the pump
4 control module in response to the pressure determinations of
the pressure determining module. The response determination
~ module generates an alann and initlates maximal cont~nuous
7 aspiration by both infusion and aspiration pumps in response
8 to a number o intra-gallbladder pressure conditions
g including: no pressure variations of a predetermined ampl~tude
detected for a predetermined period of time; abnormal pressure
11 detected for a predetermined period of time or after
12 predetermined volume has been used to purge said aspiration
13 lumen; more than a predetermined number of purge cycles
14 occurring within a predetermined period of time; detected
1~ pressure remaining less than a lower set limit for a
16 predetermined period of time or the system being unable to
17 maintain the pressure within normal range for a predetermined
18 period of time.
19 The response determination module also stops infusion and
maintains aspiration in response to intra-gallhladder pressure
21 exceeding an upper set limit and aspirates through the
22 infusion lumen until the pressure falls to an acceptable
23 ran~e. The response determination module then reYerses flow
24 to purge the aspiration lumen~ The module also stops
2S aspiration in response to the condltion wherein the pressure
26 is less than the lower set limit.
27 Another aspect of the invention is a means Por
28 continuously measuring tha pressure within the gallbladder of
29 a patient and a means for controlling the in~usion and
aspiration of a solvent into the gallbladder ill response So
31 those measurements to maintain said pre.ssure within the set
32 limits.
33 A further feature of the invention i5 a method for
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1 dissolution of gallstones comprising the-steps of continuously
2 measuring the pressure within the gallbladder of a patient and
3 contrnlling the infusion and aspiration of a solvent into the
4 gallbladder in response to those measurements. The method
further comprises the step of periodically measuring the
6 amount of cholesterol in the solvent ~nd replacing tha solvent
7 when the cholesterol concentration in the solvent reaches a
8 predetermined concentration limit.
g The method further comprlses, prior to introduct~on oP
10 solvent into the gallbladder, the ~easuring of a critical ,;;,
ll leakage pressure at which fluid in the ~allbladder discharges
12 into an adjacent part of the body, and using the value oP that
13 pressure for controlling the in~usion and aspiration. T h e
14 st~p of measuring the critlcal leakage pressure ~omprises the
injection into th~ gallbladder o~ a radiopaque dye at
16 increasing pressure until the disch~rge of th~ dye is observed
17 radiographically. The amount of pressure required to cause
18 the leakage of dye i5 recorded as the critical leakage
19 pressure and the amount of fluid required to rill the
gallbladder is the available volume. The step of infusing the
21 solvent into the gallbladder occurs at a rate sufficient to
22 create solvent turbulence adjacent the gallstones.
23 An aspect of the invention furtb r includes a ~ystem,
24 including a sy~tem bus; a microprocessor in communic~tion with
the system bus; a ~emory for holding algorithms, the memory
26 in communication with the system bus; an analog to digital
27 converter having an input terminal for receiving an analog
28 signal representative of the intra-gallbladder pressure and !
29 an output terminal ~or applying digital signals representing
the pressure on said system bus; a pressure transducer having
31 a precsuxe sensor and an output terminal, the output terminal
32 af the pressure transducer in communication with the input
33 terminal of the analog to digital converter. The pressure
WO ~1/12g~1) Pcr/us~/n~037
l tran~u~er generates a pressure signal related to the pressure
2 of the solvent within the gallbladder.
3 The system also includes ~ res~ervoir, for filling with
4 a gallstone dissolving solvent, an infusion pump connected by
conduits to pu~p solvent from the reservoir into the
6 gallbladder, and an aspiration pump connected by conduits to
7 wi~hdraw solvent from the gallbladder and discharge the
8 solvent back into the reservolr. The system further includes
9 a pump controller having an input terminal in communication
with the system bu~ and a plurality of output terminals, on~
~1 of said output terminals in communication with the aspiration
12 pump and one of said output terminals in communication with
13 tAe infusion pump, the microprocessor controlling said pump
14 con~roller, which in turn controls the aspiration and infusion
pumps in respon~ie to signals received from said pressure
~6 transducer. The microprocessor terminates infusion and
17 initiates aspiration in response to signals indicating excess
18 pressure in the gallbladder.
19 hdditionally, the system also includes a catheter having
20 a plurality of lumens, a first one of the lumens connected at
~1 its proximal end to the infusion pump; a second one of the
22 lumens c~nnected at its pr~xlmal end to the aspiration pumpi
23 and a means to sens~ lntra gallbladder fluid pressure
24 as~ociated with the distal portion of the catheter for
continuously providing an indication of the pressure of
26 fluid to the pressure transducer.
27 Yet another aspect of the invention is the ability to
28 safely dissolve gallstones when pressure measurements are
29 uncertain by infusing and aspirating intermittently a volume
of solvent which is less than the available volume of the
31 gallbladder.
32
33 BRIElii' DESCRIPTION OF THE DRAWINGS
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1 Figure 1 is a sch~matic diagram of an apparatUs suitable
2 for delivering solvent to a gallbladder and for removing the
3 solv~nt containing dissolved or fragm~e~ted gallbladder stones.
4 Figure 2 is a schematic diagram of a controller circuit
that regulates the pump units shown in Figure 1, as well as
6 other features of the apparatus.
7 Figures 3, 4 and 5 show features of a three-lumen
8 catheter, Figure 3 being a sectionaL YieW taken on 1 ine 3-3
9 of Figure 4.
Figure 6 is a schematic diagram of another embodiment of
11 the apparatus.
12 Figures 7 and 8 show features of another suitable three-
13 lumen catheter, with Fi~ure 8 being ~ eectional view take~ on
14 line ~-8 of Pigure 7~
Figure 9 is a schematic diagram of an embcdlment of the
1~ catheter portion O~ the i~Vention in the ~or~ of a pigtail
17 catheter, Figure 9A ls a cross-sectional view o the catheter
18 of Figure 9 taken through lirle 9A-9A.
19 Figure lO i~ a block diagram of an embo~i~ent o~ the
apparatus wherein a microprocessor controls the s::omponents of
21 the apparatus.
22 Figure 11 i5 a schematic diagram of the cathetsr of the
23 lnvention positioned within the gall bladder of a patient.
24 Figure 12 is a flow diagram of an embodiment of the
2 5 algorithm of the invention depicted in Figure lo. Figure 12A
26 is a flow diagram of the start pumps subroutine of the
27 algorithm of ~igure 12 . Figure 12B is a flow diagram o~ the
28 purge subroutine of figurP 12. Figure 12C is a 1OW diagram
29 ~ of th~ alarm subroutine of figure 12. Figure l~D is a flow
30 diagram of the check pressure limits subroutine o~ figure 12.
31 Figure 12E is a ~low diagram of the control pumps subroutine
32 of f igure 12 .
33
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1 DETAILED DESCRIPTION OF THE INVENTIQN
2 The inventi~n described herein is suitably employed for
3 deli~ering fluids (solvents) to organs for removing
4 obstructions contained therein. It: will be appreciated at the
outset that, while the subject invention described below
6 de~ails the inventton regarding the removal of gallstone~ rom
7 the gallbladder, the lnvention can be used to remove a variety
8 o~ obstructions from bodily cavitiles or organs other than the
9 gallbladder, and ~hus should not be construed as being
narrowly limited to the treatment of gallstones. Indeed, it
11 will become readily apparent that the device is easily adapted
12 to removing obstructions from organ~ or bodily ca~ities in
13 general.
14 The invention described herein is an organ pressure
sensitive apparatus having a ~olvent delive~y mean~ in
16 constant communica-ion with a controller circuit via one or
17 more pressure transducers th~t monitor the intra-organ
~8 pressure.
19 The pressure transducer may be positioned either within
the gallbladder itself or external to the patient at the
21 proximal end of a fluid filled column whose distal end is
22 placed within the gallbladder. This can be accompli~h~d by
23 using the pressur~ sensing lumen either æs the fluid fllled
24 column or as the in situ location of the pressure sensing
transducer itself. A variety of pressure transducers are
26 available for both _in_situ and fluid column use. In situ
27 transducers need be small and capable of ~ithstanding the
28 effects oP the solvent. Suitabl~ tran~ducers include but are
29 not limited to fiber optic pressure sensors, piezoelectric
prPssure sensors and capacitative sensors. The wlres or
31 fibers of an in situ transducer pass through khe separate
32 pressure sensing lumen or through either of the solvent flow
33 lumens or may be embedded in the catheter wall. A suitable
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1 transducer for use on the proximal end of the fluid column is
2 a Statham Gould pressure transducer P23ID. When using an in
3 situ transducer, it is possible to have the transducer
4 remo~able from and insertable into the catheter once the
catheter is in position within the gallbladder. I~ this way,
6 the transdu~er can be replaced during th~ proc~dure.
7 Additionally, such an insertable transducer would permit the
8 use of a smaller catheter for the same amount of fluid flow
g since it could be placed in one of the flow lumens. The
apparatus functions over a preset pressure range delivering
11 fluid to the gallbladder, causing the ~luid to contact and
12 dissolve the gallstones, and withdrawing fluid from the
13 gallbladder, thereby accompllshing the removal of dissolved
14 or fragmented gallstones. The rate of solvent delivery ~nd
removal ca~ be adjusted to create the necessary turbulence to
16 dissolve or fragment gallstones. If the pressure exceeds that
17 of the normal operating range, the apparatus diverts solvent
18 from the organ, thereby preventing le~kage of the solvent fr~m
19 the sitP of treatment. Further, above the normal operating
pressure range, the apparatus can be progr~mmed to be "self-
Zl purging". This may be desirable in the instance when the
22 obstruction is only partially dissolvable, causing blockage
23 of the sol~ent removal or aspiration means. Rt pressures
24 below the normal operating pressure range, the rate of
aspiration is decreased while infusion continues, thereby
26 reestablishing normal operating pressur~.
27 Dissolution time is minimized by operation at high
28 solvent flow rates. The maximum.flow is attained when the
29 instantaneous infusion flow matches the instantaneous
aspir~tion flow. At such a null point, neither pump is slowed
31 down ~r shut off by the pressure deter,mining algorithm. A
32 feature of this in~ention is the calibration of the pump
33 . catheter sy~tem in both infusion and aspiration, hence
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1 gener~tinq a flow vs. control ~oltage relationship for both
pump~. An input parameter is the desired flow r-ate. The
3 microFL-ocessor will not accept values which can not be
4 attain~d by both pumps and operate~ both pumps at the desired
flow rates when the pressure is in the vicinity of the
6 pressure set point. As pressure rises above the set point the
7 aspiration pump speed is increased and as the pressure falls
8 below the set point the aspiration pump speed decreases thus
9 possessing an ability to dri~e the system to the set point~
During a procedure, the flow rate may be increased to a value
11 limited by either the aspiration, or infusion lumen, or the
12 size and compliance of the patient's gallbladder and/or the
13 attendant pressure excursions experienced.
14 A key consideration with regard to the organ pressure~
sensiti~e aspects of the syste~ is the realization that
16 leakage of solvent from the gallbladder occurs when the
17 intraluminal pressure exceeds that in the cystic duct, common
18 bile duct or ampulla (whichever is selected for the procedure
19 in a particular patient) and that neither the gallbladder
~0 volume per se nor the flow rate of solvent per se are
21 intimately involved. This in tUrn leads to recogni~ion ~hat
22 critical leakage pressure from the gallbladder differs from
23 patient to patient, and that leakage is a function not only
24 of solvent delivery but natural gallbladder contractions or
external pressures to the gallbladder. The subject invention
26 take~ into account those pressure changes that are of
27 sufficient duration or strength to affect solvent leakage.
28 Because the critical leakage pressure from the
29 gallbladder differs from patient to patient, it is important
to determine the critical leakage pressure for each individual
31 patient. To determine this pressure, a catheter is introduced
32 into the gallbladcler and, under fluoroscopy, a contrast
33 material is injected into the gallbladder with increasing
~ 3~) PCT/~S~1/01~37
1 pressure. The pressure at which the contrast medium enters
2 the intestine or leaks at the percutaneous entry point is the
3 critical lea~a~e pressure. As the gallbladder fills, its
4 pressure will increase until contrast medium is observed
radiographically to flow through the cystic duct into the
6 common bile duct or leak at the percutaneous entry site. The
7 volume of dye present in the gallbladder at this pressure is
8 the a~ailable volume. This critical leakage pressure , or a
9 safety pressure below the critical leakage pressure I and, if
desired, the available volume are entered as parameters in the
11 controller. From the critical leakage pressure value, the
12 high pressure or maximum operating point or upper set limit is
13 determined.
14 Typically, the maximum operating pressure is set at 75%
to 9~% of the measured critical leakage pressure, and the
16 maximum pressure alarm is typically 8S%-95% of the critical
17 leakage pressure.
18 To determine the mlnimum operating pressure or lower set
19 limit, the contrast medium is aspirated from the gallbladder.
As ~he pressure inside thei gallbladder falls, bile will
21 eventually begin being aspirated into the gallbladder from the
22 common bile duct. The pressure at which this occurs i the
23 bile aspiration pressure. The minimum operating pressure or
24 lower set limit is typically set 2 to 10 cm of water above the
bile aspiration pressure to minimize solvent dilution with
26 bile. The minimum alarm pressure is set slightly belo~ the
27 bile aspiration pressure.
28 Accurate measurements of volumemetric flow, to and from
29 the gallbladder, will permit the calculation of net fluid
retained in the patient. The signal of net volume of retained
31 fluid can be used as a backup safety check when pressure
32 measurements are controlling the pumps or as a primary control
33 msde when pressure measurements are not possible, e.g., an
7.
' ,:
3n PCr/~lS'~1/01037
17 ~ t~
1 aberr~nt c~stic duct, with no valves of Heister. To benefit
from .olumetric flow measurements, pumping should be initiated
3 when the aallbladder is evacuated. When the net retained flow
4 approachec the predetermined gal:lbladder volume, an alarm
should be established or net aspiration should be increased.
6 Figure 1 shows an exemplary app~ratus for removing
7 gallstones. Reservoir 10 contains a solvent that is a
8 chemical suitable for dissolving gallstones. Should the
9 gallstone be composed of choleste:rol, a variety of solvents
would be efficacious. Particularly effective is methyl ter~-
11 butyl ether (MTBE). The latter has been shown to r~adily
12 dissolve cholesterol stones rapidly both in vitro and in vivo.
13 At normal operating pressures, the solvent moves via a conduit
14 12 from the reservoir 10 by aid of a first pump 14. The fluid
then moves through a valve 16 and from the ~alve through
16 infusion port 17 in a catheter 19 into t~e gallbladder.
17 Durinq this operation valve 2 6 is closed to prevent solvent
18 return to reservoir. The solvent is delivered at a
19 predet~rmined effective rate for gallstone dissolution thereby
providing solvent turbulence and contact with the gallstones
21 for a period of time sufficient for effective gallstone
22 dissolution or fragmentation and fragment removal.
2~ Simultaneously with the delivery oP MTBE to the
24 gallbladder, a second pump 18 aspirates the fluid from the
25 gallbladder now containing dissolved gallstones and debris. .
26 This material passes out of the gallbladder via an aspiration
27 port ~0 in the catheter. The fluid is pumped from the
28 gallbladder by pump 18, passing through valve 23, and from
29 there it is deposited in a receiver reservoir. Either
reservoir 10 used as the sourc~ of the solvent or a separate
31 reservoir is suitable for this purpose. Figure 1 shows the
32 same reservoir 10 being utilized as both the sourc~ of fluid
33 passed to the gallbladder and as the receiver of aspirated
~ x3n ^~' PC~/US91/0]037
l flui(l therefrom. It is worth noting that if the same
reser-~oir is used, gallbladder stone fragments, bile, mucous
3 and th~ e removed from the gallbladder are heavier than the
4 solvent, MTBE, and therefore settle to the bottom of the
reservoir and do not hinder continued withdrawal of
6 essentially pure fluid from the reservoir to effect further
7 stone dissolutlon.
8 ln the case where a single reservoir is used to supply
9 the solvent and receive the aspirat:ed fluid, the fluid should
lo be periodically sampled and the cholesterol concentration in
11 the MTBE measured. Since the heavy debris falls to the bottom
12 of the reservoir, the sample of the ~luid should be taken of
13 the fluid from the upper portion of the reservoir. The sample
14 can then be tested to determine the cholesterol concentration
level, for example by spectrophotom~tryO ~he fluid should be
16 removed and replaced when the rholesterol concentration
17 reaches a predetermined level ~e.g. about 30%). It should be
18 noted that higher or lower concentration levels of cholesterol
19 in the solvent only effect the efficiency of dissolutionO
Further, in a single reservoir system, since the
21 aspiration rate and the infusion r~te are in general not
22 equal, there is a provision to vent the reservoir. The
23 venting method should not allow the flammable fumes of ~he
24 solvent to escape. An alternative way o~ compensa'cing for
rate differences is the use o a solvent resistant bladder for
26 the reservoir. Such a bladder expands or contracts as the
27 volume of fluid contained within it changes. This form of t.
28 closed reservoir prevents fumes rom escaping.
29 The pumps 14 and 18 are controlled by a controllPr
circuit 22. The controller circuit 22 in turn receives
31 pressul-e readings from the transducer 24 causing the
32 controller circuit 22 to open or close flow valves 16 ,. 23 and
33 26 to inhibit infusion or aspiration as necessary to control
, . . . .. ~ . , . ,, :
w~ 3n 1~CT/I'S91/01037
- 19 2~
l organ pressure depending on whether the transducer 24
2 indicate~ that the pressure in the gallbladder is within,
3 above, or below the normal operating pressure range. The
4 transducer in turn senses the gallbladder fluid pressure by
c~mmunication through port 28 of the catheter 19.
6 At the normal operating pressur~, first pump l~ dellvers
7 fluid from reservoir lO through tube 12 and valve 16 to the
8 gallbladder. Simultaneously, and at a slightly slower rate,
9 second pump 18 aspirates the fluid from the gallbladder
through catheter aspiration port 20. Fluid passes throuyh the
ll valve 23 and thence through conduit 25 to the reservoir lO.
12 Conduit 12, catheter l9 and conduit 25 form a fluid
13 circuit connecting the source reservoir lO with the bodily
14 organ or cavity into which the catheter is inserted and then
to the- receiving reservoir (which as noted may also be
16 reser~oir lO). The pumps 14 and 18 are in the circuit, in
17 conduits 12 and 25 respectively. (For the purpose of
18 description herein, the "forward" fluid flow direction will
l9 be defined as flow in the direction of the arrows in Figures
l and 6, and "reverse" flow will be flow in the direction
21 opposite the arrows.)
22 The controller 22 is progra~med to respond to pressures
23 that exceed or are below that of the normal operating pressure
24 range Above the normal operating pressure range ("hi~h
pressure mode"), the controller 22 shuts ~own valve 16 and
26 simultaneously opens valve 26~ This provides a path for
27 diverting the incoming fluid away from the gallbladder. At
28 that time valve 23 is open to continue gallbladder emptying
23 to return the pressure to the normal operating range. If the
press~1re in the gallbladder does not return to the normal
31 operating pressure setting within a preset time, for example
32 a few seconds, then the controller 22 can be programme~ to
33 instr~1ct the pumps to reverse the direction oP Pluid movement,
~'~91/1'~3~) ~, PCT/VS91/01037
- 20 ~
l and simultaneously valves 23 and 26 are closed. The
2 controller unit is programmed to close ~alve 23 after a slight
3 dela~ ~n that a small amount of fluid, approximately l ml, can
4 pass throuah the valve before it is shut. Valve 16 is opened
to provide a path for fluid to be reverse aspirated from th~
6 gallbladder in this "self-purging" mode. This mode
7 essentially causes a small amount: of fluid to be pumped in
8 through the aspiration port 20 of the catheter l9 to clear it
g of obstructions while aspir~tion is effected by pump 14
through valve 16. The fluid which is pumped into the
11 gallbladder passes from the reservoir lO through valve 23,
12 prior to valve Z3 closing in response to high pressure present
13 in the gallbladder. Generally this will consist of about l
14 ml of fluid passing through valve 23 b~fore it shuts. This
mode of operation continues for a brief period oP time, and
16 then the controller unit 22 instructs the maçhine to resume
17 normal operation should the obstruc~ion be removed and the
18 pressure transducer 24 indicate reestablishment of the normal
l9 operating pressure range. If the transducer continues to
indicate pressures present in the gallbladder above the normal
21 operating pressure, the controller unit 22 again instructs the
22 pumping apparatus to purge the system. If, after several
23 "self purging" cycles, the obstruction is still not removed,
24 the controller unit 22 then shuts down the system and
activates an alarm circuit 34 notifying the user of a
26 potentially dangerous condition.
27 Figure 2 illustrates a representatiYe controller unit 22.
28 The controller circuit 22 inst.ucts the pumps 14 and 18 to
29 deliver or aspirate fluid from the gallbladder. Thus, a
circu.it will typically have a pressure transducer 30; such as
31 the ~tatham Gould pressure transducer P23ID, as mentioned
32 previously. The pressure transducer 30 relays information to
33 an amplification device 32 which amplifies the slgnal from the
~(>91~t7~3n PCr/US91/0103~
., .
- 21 ~
l trans~ucer 30 and transmits it to a high and low pressure
alarm circuit 34, then either directly or through the
3 aver~?ing circuit 36 to a pressure-sensing circuit 38 that
4 read~ preset low and high pressure values and which is
connected to the valves 16, 23 ancl 26. The latter valves are
6 typically solenoid flow valves or tube compression ~alves.
7 The averaging circuit 36 can be switched in if desired to
8 discriminate between pressure c'hanges in the gallbladder
9 arising from fluid ~uild~up due to obstructions or from
hyperventilating, laughing or llke activ~ties. Thus the
ll averaging circuit essentially screens out artificially high
12 or low pressure peaks which ln fact do not lead to gaillbladder
l3 emptying.
14 The pressure sensing circuit 38 is connected to a cascade
timer 40, which in turn is connected to a pump reverse relay
16 circuit 42. Thus, when gallbladder pressure exceeds that of
17 the normal operating pressure range and the obstruction is not
18 removed within a predetermined period, the cascade timer 40
l9 activates the pump reverse relay 42. T~e latter circuit is
responsible for "self-purging1' t~ie system. Should high
21 pressure persist after se~eral brief ~self purging" cycles,
22 then the alarm circuit 34 is activated, causing an initial
23 period of aspiration in the reverse mode (with valves 16 and
24 23 open and val~e 26 closed), then stopping the pumping system
by shutting off its power supply and the triggering of a
26 visual, audible or other alarm notifying the user. Note that
27 at any time during the pump reverse cycle, should the pressure
28 return to within the normal pressure range, the apparatus
29 resumeC normal operation.
It will be further noted as shown in Figure 2 that a pump
31 power relay circuit 44 and a pump speed control circuit 46 are
32 also interactive with the whole system. T~e pump speed
33 control circuit 46 derives power through the pump pow8r relay
.. .. . . ,.. .... ; . ... ~.. , . - . - .. .- .. ., . ~ -
~0 91/1~83() PCr/US~31/01037
rj ~ 7~ -- 2 2 ~
1 44, ~hich, in turn, is controlled by the alarm circuit 34.
The pump motor derives its power supply from the pump power
3 rela~ 4~. Any time an alarm condition exists, this relay
4 shutc off power to the pump, stopping it from pumping. The
s pump speed control circuit 46 has a manual adjustment
6 capability through which the operator ca~ set the desired
7 perfusion rate for that specific situation. An a~alo~
8 pressure read-out 4~ is ~rovided for the operator to assess
g effective operation and to refer to during calibration.
Alternatively, or in addition, the output can be fed to a
11 video display terminal 118 (of Fig. 10) driv~n by appropriate
12 software to provide the operator with an inter~ittent or
13 continuous display of system operating mode, pressure, etc.,
14 and may be integrated with the indicators and alarm of alarm
circuit 34.
lS Note that if desired, one or more appropria e
17 microprocessors can replace many of the components of the
18 system. Referring to Figure. 10, in a system controlled by
19 a microprocessor 100, the micropr~cessor 100 is connectQd to
the pressure transducer 24 by an analog to digital converter
21 (A/D~ 116 connected to the system bus 122. The A/D converter
22 116 changes the pre~sure transducer's 24 analog signals to
23 digital signals for processing. Con~rol of the pumps is
24 accomplished by the microprocessor 100 through a
digital/analog converter (~/A) 112, if the pump controller
26 tPC) 124 requires analog signals, or through a digital
27 parallel or serial interface (P/SI) 114 if the pump controller
28 124 is capable of responding to digital signals. The D~A 112
29 or the P/SI 114 can also be used to control the solenoid
valvec 16 (only one shown for purposes of illustration).
31 The digital data is processed by the microprocessor 100
32 which ~ecutes algorithms located in memory 110 to perform the
33 functions otherwise performed by components of the pressure
W~l/t'~3() PCr/VS~1/0l037
I - 23 ~ 2 ~ ~ 3c~ ~
1 sensinq circuit shown in Fig. 2. Specifically, the
~ micro~rocessor 100 by itself replaces the high and low
3 pressure detector 34, the signal averager 36, and the cascade
4 timer 40. The microprocessor 100 in ~onjunction with the A/D
converter 116 replaces the pressure sensing portion of the
6 pressure sensing and solenoid control interface 38, while the
7 microprocessor 100 in conjunction with the D/~ 112 or P/SI 114
8 replaces the solenoid portion of t~e pressure sensing and
9 solenoid control ~nterface 38. Further, dapending upon the
form of the controller 124 actually controlling the pumps 14,
11 18, the microprocessor 100 and A/D 116 or P/SI 114 also may
12 replace the pump power relay 44, speed control circuit 46, and
13 pump reverse relay 42.
14 Figure 6 illustrates another alternative embodiment of
the apparatus, which eliminates the valves by having separate
16 control of the two pumps 14 and 18. Each pump motor has its
17 own DC drive 47 and 45 respectively. Both drives are
18 controlled by controller 22', which has an appropriate
19 microprocessor to control the speed of each motor (and thus
the flow rate of each pump) in response to the pressure
21 signals from transducer 24. Thus instead of opening and
22 closing valves to effect the proper infusion, aspiration or
23 purging, the controller 22~ regulates each pump's flow rate
24 and directivn of flow.
This embodiment has the advantage that all fluid conduits
26 (tubing, catheter, reservoir) can be made of easily
27 replaceable material. Thus each patient can be treated using
28 a system in which all wettable surfaces are limi~ed in use
29 solel~ to that one patient and one treating session. Again
many of the components of this embodiment can also be replaced
31 with ~ microprocessor system.
32 There are several features of the apparatus that enhance
33 its performance. The pumps preferred in the subject invention
,
~ 3~) PC~/U59l/01037
~ , ~, . ~
- 24 -
1 are ~ristaltic pumps. This type of pump offers s~veral
2 advant~g~ such as the replaceable wettable surfaces mentioned
3 above, which in addition to their individual sterility will
4 be p~rticularly advantageous in those instances where the
solvent being used to dissolve l:he obstructiorl is at all
6 corrosive- Moreover, peristaltic pumps are resistant to
7 clogging, in contrast to standard syringe type pumps.
8 However, it should be noted that ~yri~ge pumps are similarly
9 employable in the subject invention in those instances ~hPre
the fluid used to dissolve and remove the obstruction is a
11 solvent, provided that the syringe pumps are constru~ted of
12 suitable material, preferably polytetrafluoroethylene (PTFE)
13 or glass. Syringe pumps made of plastic are not preferred in
14 instances where the solvents used are incompatible with the
plastic compositio~ of the syringe. An addi~ional
16 disad~antage associated with the use of syringe pumps that is
17 not present in peristaltic pumps is that in those instances
18 where a solvent is being utilized, evaporation of the solvent
19 from between the plunger and the body can cause deposits in
the body of the syringe, causing it to "freeze" and thus
21 interrupt deliv~ry of the ~luid to the orga~ being treated.
22 Lastly, peristaltic pumps are capable of much greater fluid
23 circulation rates than ar~ syringe pumps. This is
24 advantageous in certain instances where ~he obstruction ~o be
removed, such as a gallstone, requires turbul~nt flow rates
26 across the surface of the gallstone to accelerate th~
27 dissolution process.
28 A predetermined normal operating pressure range is
29 programmed into the controller circuit ~2. Should the
pressure in the gallbladder exceed normal operating pressure,
31 the action of the controller circuit 22 prevents leakage of
32 solvel~t from the gallbladder through the cystic duct in o the
33 commor~ ductj as well as into the intestine or around the entry
... , , .. .. .. ~
~vn ~ 3~ ^''~ ~ ^ PCT/U$91/010~7
;~ - 25 -
l site of the catheter. Also, because the controller circuit
2 "seeC'- true gallbladder pressure, it readily adjusts to
3 decre~se a~ well as increase pressure by adjusting the net
4 deli~er~ rate of the solvent to the gallbladder. For example,
should the pressure fall below the normal operating pressure
6 range, the controller circuit 22 ceases or slows down the rate
7 of aspiration of solvent, and simultaneously con~inues
8 infusing solvent to reestablish normal operating pressure.
g The pressure sensitive ala~n circuit 34 is constantly
comparing the system's set operating pressures and the
ll gallbladder pressure. If gallbladder pressure cannot be
12 brought into ~he normal operating pressure range by the action
13 of the controller circuit 22 in a specified period of time,
14 it will revert to a period of maximal aspiration, then shut
down the pumping system and sound an alarm drawing the
16 attention of the operator. The operator, after correcting the
17 problem, can resume normal operation by activating the reset
18 button 49.
l9 Referring to Fiqs. lO and 12, in the case of a
microprocessor system, the microprocessor lO0 monitors the
21 pressure values produced by the transducer 24 and controls the
22 pumps 14, 18, and valves 16 in response to those pressure
23 values according to an algorithm stored in the system memory
24 llO. The algorithm can be generally partitioned into a module
for periodically making pressure measurements, a module for
26 controlling pump speed and direction and a module for
27 determining the proper response to the various pressure
28 measurements.
29 The module for determining the proper response to the
various pressure measurements checks several conditions. If
3l there are no variations of a predetermined amplitude in the
32 measur~d pressure for a predetermined amount of time, the
33 mvdule assumes that either the pressure lumen is blocked or
...
~.,
~')~ 3~ ~ 26 - rc~/us9~ 7
1 that the pressure measurement subsystem has failed and sets
2 an al~lm condition. The setting of an alarm condition causes
3 the ~mp control module to set maximal continuous aspiration
4 by both pumps and to sound an alarm.
If the pressure measured is greater than th~ upper set
6 limit, the pressure measuring ~odule instructs t~e pump
7 control module to stop the infusion pump and cause the
8 aspiration pump to maintain aspiration. If the pressure
g continues to remain above the upper set limit for more than
a predetermined amount of time, the module a5sumes that th~.re
11 is a blockage in the aspiration openings or lumen. In
12 response to this condition, the pump control module instructs
13 the pump normally used for infuslon to aspirate. When the
14 pressure falls to the lower set limit, the pump control module
15 instru~ts the pump normally used for aspirat~on to switch to
16 infusion and the p~lmp normally used for infusion to swi~ch to
17 aspiration i~ an attempt to purge the side holes and lumien.
18 If the operating pressure does not return to normal within a
19 predetermined amount of time or after a predet~irmined volume
has been used to purge the aspiration openings and lumen, an
21 alarm condition is set by the response determination module.
22 Further, if there are more than a predetermin~d number of
~3 purge cycles within a predetermined period of time, the
24 response determination module sets an alarm condition.
If the pressure measured ls less than the lower set
Z6 limit, aspiration is stopped, and if the pressure remains less
27 than the lower set limit for a predetermined amount of ~ime,
28 an alarm condition is set. Finally, i~ the system is unable
29 to operate within its normal range for a predetermined amount
of time, an alarm condition is also set.
3l Figure 12 is a flow diagram of the main program loop of
32 an embodiment of the algorithm used to determine the proper
33 response to various pressure measurements. Figures 12A-12E
~091/1~3n P(-r/~lS91/0~037
~ 27
1 are flow diagrams of subroutines executed during the main
2 program loop. The main program calls the CHECK-PRESSURE-
3 LIMIT~ subroutine 150 which in turn calls a series of other
4 subro~1tines to perform specific functions when the pressures
and/or time delays are outside the desired ranges, and when
6 the pressure is above the upper pressure limit or below the
7 lower pressure limit. Within the desired pressure range, the
8 CONTROL PUMPS subroutine 152 operates the pumps in a
9 proportional fashion in an attempt to stay within th~ pressure
limits. The main program begins by the operator entering the
11 operating parameters (operating pressures, alarm pressures,
12 etc.) into the system by the system keyboard and ~hen calling
13 the START-PUMPS subroutine 149.
14 When the main program is executed for the first time
durin~ the procedure, or when the pumps have been stopped ~nd
16 must be restarted the subroutine START-PUMPS is called.
17 Referring to Figure 12A, the purpose of the START-PUMPS
18 subroutine is to determine from the present pressure
19 measurement which pump should be started. That is, if the
pressure is high initially, only aspiration should oocur,
21 while if the pressure is low only infusion should occur.
22 Further, should the system be unable to come to the proper
23 pressure operating range within a fixed amount of time, an
24 alarm condition exists and the operator should be notified.
To accomplish this, the subroutine begins by determining if
26 the ~ressure in the gallbladder is greater than the lower
27 operating pressure limit 160 and if the pressure is not
28 greater, then the infusion pump is turned on and the
29 aspir~tion pump remains off 166. If the pressure is greater,
the infusion pump r~mains off, the aspiration pump is turned
31 on 162, an aspiration timer is started, and the pressure is
32 compare~ to the lower operating pressure limit again 163. If
33 the p~essure is still above the lower operating limit 163, the
~01)1/12~3(1 ,`~` Pcr/ussl/olu
- 28 -
l el~p~ time from the start of aspiration as indicated by the
2 aspir~tion timer is compared 164 to the maximum aspiration
3 time ~llowed parameter. If the elapsed time is less than the
4 maximum aspiration time allowed, the pressure is again
compar~d with the lower operating pressure limit 163. If the
6 elapsed time is greater than the maximum allowed then
7 aspiration has failed to reduce the pressure and the alarm
8 subroutine is called in an alarm 0) condition l65.
9 I f the pressure is below the lower operating pressure
limit 163, the infusion pump is turned on, the aspiration pump
ll is turned off, the aspiration timer i5 cleared, an infusion
12 timer is started and the pressure compared to th~ upper
13 operating pressure limit 168. If the pressure is less than
14 the upper operating pressure the elapsed time of infusion is
compared to th~ maximum infusion time parameter 17S. If the
16 elapsed time is greater than the allowed time 17~, indicating
17 a lea~age of solvent out of the gallbladder, the alarm
18 subroutine is called in an alarm (0) condition 178.
l9 If the pressure is qreater than the upper operating
pressure limit, the infusion pump is turned off, the
21 aspiration pump is turned on, the infusion timer is cleared,
22 and the aspiration timer is again started. The pressure is
23 again compared to the lower operating limit l84 and if it is
24 less than the lower operating limit, the aspiration timer is
cleared, the infusion pump i5 turned on and the aspiration
26 pump is turned off 187.
27 If the pressure exceeds the lower operating pressurP
28 limit 184, the aspiration timer is compared to the maximum
29 aspiration time parameter 186 and if the elapsed time exceeds
the maximum time allowed, indicating that aspiration is unable
3l to reduce the pressure, the alarm subroutine is called in the
32 alarm (0) condition. If the elapsed time is less than the
33 maximum aspirati.on time, the pressure comparison cycle is
: :
. - , - . , ~ .;. . . ., . . ,,, .. :: ., . ., , . , . . . : ..
~-091/1'830 . PCT/US~3/01037
- 29 - J ~ 8 ~
l repeato~ 1~4.
~ Once the infusion pump is on and the aspiration pump is
3 off 1~7. the pressure is compared to the operating set
4 pres~re l89 and if it is less, the pressure comparison loop
is repeated. If the pressure exceeds the operating point the
6 subroutine simply returns to the ~ain routine.
7 When the it is determined that the aspiration pump is
8 unable to aspirate sufficiently t:o maintain pressure within
9 the requisite range below the upper pressure limit, the CHECX
PRESSURE subroutine causes both pumps to maximally aspirate,
ll and if the lower pressure limit can be attained and the
12 allowed number of purges have not be n exceeded 314, 326, 328
13 322 and 330 of Fig. 12D, it is assumed that the aspiration
14 port is blocked and that a purge should be attempted. Th
PUR~E subroutine is called to reverse flow through the
16 aspiration and i~fusion lumens in an attempt to clear the
17 aspiration lumen. Referring to Figure 12B, the PURGE
18 subroutine first starts a purge timer 196, and sets both the
l9 infusion and aspiration pumps in reverse 192, 194 at the set
flow rates in an attempt to clsar the aspiration lumen. The
21 elapsed time from the purge timer is compared 196 to the purge
22 cycle period, and the purge cycle is allowed to continue if
23 the elapsed time indicated by the purge timer is less than the
24 purge cycle period and the pressure of the fluid in ~he
gallbladder is less than the upper opérating pressure limit
26 parameter 198. If the pressure is less than the upper
27 operating pressure limit, the purge continues and the elapsed
28 time compared 196 again. If the pressure exceeds the upper
29 pressure limit 198, the program will proceed through decision
point 200, and the pressure check subroutine which will cause
31 maximum aspiration and ano~her purge cycle again if the number
32 of purge cycles has not been exceeded.
33 If the purge cycle time is exceeded without exceeding the
- , .. , - ~., , . , , ., . . ~. . . . .
-'091/l2~3~) ~u~i P~r/us~ ~/01037
~, ~, . ~,
1 ~ppeL- pressure limit, the pressure is compared to the
operating set point 200. If the pressure is below the set
3 point, the aspiration pump is stopped 202, and the infusion
4 pump i~ operated at set point in the forward direction. If
the pressure does not attain the operating set point 206
6 within the maximum infusion time, the system calls alar~
7 subro~tine 212 in an alarm (1~ state. If the operating set
~ point is attained within the time parameter 210, the system
9 returns to the operate cycle ~hrough 224 and 22~.
If, upon the completion of time 196, the pressure is
11 above the set point, the infusion and aspiration pumps are
12 turned on in the forward dir2ction 224, 226 and ~he program
13 returns to the operate cycle.
14 There are two alarm conditions depending upon
whether an abnormal pressure condition is recoverable (alarm
16 (1) condition) or whether the condition is so hazardous that
17 normal operation should not be resumed (alarmi (0) condition).
18 In either case the first priority is to aspirate Prom bo~h
19 lumen to reduce the pressure. I~ the lower pressure limit can
be attained within the alar~ aspiration ti~e, an alarm ~13
21 condition occurs and normal operations are resumed. I the
22 condition is an alarm (0), a warning is yiven and the operator
23 must intervene to stop aspiration, Referriny to Fig. 12C, the
24 ALARM subroutine, is entered in one of two states: alarm (0)
252, and alarm (1) 250. In elther state, the infusion pump
26 is set to maximum reverse 254, 256 while the aspiration pump
27 is set to maximum forward 258, 260 to generate maximum
23 aspiration. If the alarm (0~ state 252 was entered, a tone
29 is set 266, and aspiration is continued until the pumps are
stopped by operator intervention 270. No further pumping
31 occur~ until the pumps are manually restar~ed ~74.
32 lf the alarm (1) state 250 was entered, a timer is
33 started and the pressure is compare to the lower operating
~9l/l'~30 PCT/US91/0iO37
~. i'.~'LI 3l
~ pressl~re ~nd if it is less than the lower operating pressure,
2 the pumps are set to operate normally, infusing fluid 268
3 throuah the infusi~n lumen and aspirating fluid 272 from the
4 aspir~tion lumen. If the pressure is above the lower
operating pressure, the elapsed time of maximum aspiration is
S compared to a parameter which determines the maximum time
7 allowable at maximum aspiration and if that time has not be~Pn
8 reached the pressure is compared again 262. If the elapsed
9 time exceeds the maximum time allvwed, a tone is set 266, the
pumps continue to aspirate at maximum rate untll they are
11 stopped 270 by manual intervention. No pumping commences
12 until the pumps are restarted manually 274.
13 The CHECK-PRESSURE-LIMITS subroutine is called by the
14 main routine to determine the proper response to the current
lS pressure. Referring to figure l2D/ the CHECK-PRESSURE-LIMITS
16 subroutine begins by starting a timer to measure elapsed time
17 and calculating the pressure change in the last three seconds.
18 If the pressure change is less than l torr, it is assumed that
l9 the ~ressure transducer is not operating correctly and the
alarm subroutine is called in the alarm (0) state. If the
21 pressure change is greater than l torr, the pressur~ is
22 compared to the minimum alarm pressure 304 and if the pressure
23 is less than the minimum alarm pressure, the elapsed time
24 indicated by the timer is compared to the minimum alarm
pressure trigger time parameter 306. If the time is greater
26 than the minimum alarm pressure trigger time, then, the
27 pressure has been below the minimum allowable pressure for too
28 long, and the alarm subroutine is called in the alarm (0)
29 s~ate. If the time is less than the minimum pressure alarm
trigger time, the pressure is compared 310 to the maximum
31 alarm pressure and if it is less the maximum alarm pressure
32 is compared to the upper pressure limit 3i8.
33 In either case, the elapsed time is compared to the upper
.
~VO9T/12830 PCT/US91/0l037
~Q ;~ 32 -
l press~re alarm trigger time 312 or upper pressure delay time
2 320 ~n~ if the upper pressure alarm trigger time is exceeded,
3 the number of purges is compared to the number allowed 314 and
if to~ many purges have occurred, the alarm subroutine i~
called in the alarm ~0) state 316.
6 If the number of purges has not been ~xceeded, the
7 aspirate pump is set to maximu~ flow 326. The infusion pump
B is reversed and ~et to maximum flow 328, and the counter of
9 the number of purges is incremented. The pressure is then
compared to the lower pressure limit 322. If the pressure is
ll below the lower limit within the alarm aspiration time 324 a
12 purge cycle is performed 330, if not the alarm subroutine is
13 called 332 in an alarm (0) state.
14 If the pressure is below the alarm pressure 310 and the
lS upper pressure limit 318, the pressures are within the desired
16 lim~its and the system returns to the operate cycle.
17 When the pressure ~s below the upper limit and above the
18 lower limit, the CONTROL PUMPS subroutine con rols the pumps.
l9 Referring the Fig. 12E, the infusion pump will operate until
the upper limit is a~tained 340, 342. The aspiration pump is
21 turned off upon the attainment of the lower limit 346, 352.
22 At pressures between the lower limit and 85% of the set point
23 pressure, the aspiration pump operat~s at 80% of set flow,
24 348, 354. At pressures between 115% of set pressure and the
upper pressure limi~, the aspiration pump operates at 200% of
26 set flow, or maximum flow whichever is low~r 350, 356. When
27 the pressure is + 15% of the set pressure, both pumps operate
28 at set flow 358, 344.
29 The apparatus is completely automatic and is operable
without any significant operator input beyond the critical
31 pressure and available volume. Mor~over, it is readily
32 converted to a completely closed circuit system in those
33 insta~ces where the therapeutic fluid is combustible. Thi~
~.
. : .
3n PCr/VS'Jl/~)1()37
~ 33 - ~ ~8~f8~ ~
1 featu~ is required for particularly c~mbustible solvents.
2 An~ of a number of types of tubing is suitably used with
3 the ~umps of the subject apparatus. However, we have found
4 that tubing composed of "Tygon Special Formulation F~4040A"
(a ~ inyl material) or "Nalgene" (a polyurethane) is
6 particularly compatible with solvents such as methyl tert
7 butyl ether. Moreover, tubing with a large internal diameter
8 is favored for use with peristaltic pumps, enabling a high
9 volume per revolution ratio to be obtained, thereby permitting
a low revolution per minute rate to be utilized, hence
11 minimizing torque build-up when a switch over to the high
12 pressure mode leads to pump motor reverse.
13 As discussed above, the subject apparatus can be utili~ed
14 for removing obstructions in a variety of organs. However,
in the instance where it is used to remove gallstones from
16 gallbladders, perfusion rates of about 50 ml~min to 300 ml/min
17 are ~enerally more effective. This is readily accomplished
18 by manually adjusting the pump speed control circuit 46 of
19 Fig. 2. It is important that the flow rate is ~ufficlent to
cause turbulent flow within the gallbladder. It has been
21 found that turbulence increases the ra~e of gallstone
22 dissolution and helps in remo~ing the non-dissolving
2 3 f ragments.
24 A variety of catheters usable to deliver and aspirate the
fluid can be suitably employed. The catheter must be
26 insoluble in the solvent being infused. For example, a
27 polyurethane catheter is suitable ~or use with MTBE. Three-
28 lumen catheters as shown in Figures 3 5 and 7-8 are favored
29 ~ince prPssure measurements as well as perfusion and
aspiration of the fluid can all be carried out simultaneously.
31 A suitable three-lumen catheter should have an outside
32 diameter not larger than can be readily employed for the
33 surgi~al insertion of the catheter into the gallbladder, and
W~91/~3n ; 1~. PCT/US91/01037
? `~!J`'
l shoul~ ha~e an aspiration lumen 50, a pressure sensing lumen
52 and an infusion lumen 54. The aspiration lumen preferably
3 shoul~:l be larger in cross-section than the other two lumen.
4 ~or the purpose of safety, while achieving effective flow in
the system, the aspiration cross-sectional area should be
6 about 2.5 times the infusion cross-sectional area. In this
7 way, the volume removed by aspirat:ion can be greater than the
8 volume replaced by infusion under emergency conditions, while
9 allowing a substantial flow to be maintained through the
10 infusion lumen.
ll Each lumen communicates with the gallbladder through a
12 number of openings in the outside wall of the lumen. The sum
13 of the cross-sectional areas of openings to a lumen should be
14 greater than the cross-sectional area of that lumen in order
to minimize flow impedance. The cross-sectional area of each
16 opening should b~ less than the cros -sectional area of its
17 lumen to prevent debris from obstructing the lumen. The
18 aspiration and infusion openings are distributed along the
l9 length of the distal end of the cathPter. At least one
aspiration opening is located proximal to all infusion
21 openings, preferably being loc:ated at the en~-ry point of the
22 catheter into the gallbladder when th catheter 's in posit on
2~ for operation. With this configuration, aspiration takPs
24 place nearest the insertion point of the catheter into the
gallbladder. Any leakage of solvent from the gallbladder
26 throuqh the entry point of the catheter is therefore
27 immediately aspirated and does not damage surrounding tissues.
28 The aspiration lumen extends to the distal end of ~he
29 catheter and terminates in an opening at the distal end.
Referring to Fig. ll, this opening in the distal end of the
31 catheter also serves as a passageway thxough which a guidewire
32 can pass. Note that the number of openin~s is not invariant,
33 depending on the number of gallstones present in the
~() 91/1283() PCr/IJ~"1/01037
~ _ 3 5 _ ~ ~ 8 3 9 8 ;5
l gall~ dder, as well as the desirable therap~utic need to
' effect rapid treatment.
3 The distal end of the catheter is preferably curved into
4 a pi~tail shape as shown in Figure 7 to aid in its being
retained and positioned in the organ. Referring to Figs. 9
6 and 9A, such a pig-tailed catheter. can also include a string
7 74 which helps the catheter retain its pig~tailed shape since
8 fluid being pumped through the catheter and patient movement,
g coughing or sneezing tends to cause the catheter to unwind.
A monofilament or wire can be used in place of a string. The
ll retaining string can either pass through an opening 72 to its
12 own lumen 70 or can pass through the aspiration 50" or
13 infusion 54" lumen. Other means to retain the catheter within
14 the gallbladder are possible. For example, a balloon catheter
for example may s~rve to retain the catheter.
16 Since the string 74 may pass through its own lumen 52,
17 and ~ince a balloon catheter generally alss requires its own
18 lumen, the system should not be construed as being limited ~o
19 a three-lumen catheter. A Yariety of catheters of different
lumens will perform satisfactorily provided that the system
21 is modified to accommodate such catheters, such modifications
22 beinq well known to those skilled in the art.
23 When a pig-tailed catheter is used, openings to the
24 pressure lumen should be located on the inner radius of the
curve. This location provides a clear opening for accllrate
2G pressure sensing and prevents the mucosa of the gallbladder
27 from interfering with the pressure measurements.
28 8ecause this procedure can be inherently dangerous, using
29 toxic and flammable solvents, it is desired that the catheter
be use~ only with the proper pumping system. To assure this,
31 the catheter can have a structural, electrical or fiberoptic
32 connection at its proximal end which is connectable to a
33 similar structure in the remainder of the system. The system
: . .. ;, ., . : ,~ ... ~ . .:, . . :.: - .. . .. .
~V~91/1 83(~ , ~, , PCl/~J~ 103
~ 36 -
1 may therefore be prevented from functioning with an
~ inappL-~priate catheter.
3 ~t will be appreciated by those skilled in the art ~hat
4 there are numerous modifications in the electrical circuitry,
and the overall interconnecting features of the invention that
~ will achieve the efficacious removal o~ obstructions in
7 particular organs. For instance, while the automatic "self
8 purging" feature of the apparatus is desirable, a device
9 without this feature will perform adequately. Moreover, it
should be further noted that, while the invention has been
11 described as applicable to the removal o~ gallstones from
12 gallbladders, its use should not be so narrowly construed.
13 Thus, it is the intent herein to present an invention tha~ is
14 generally applicable for the removal of obstructions from a
variety of organs by dissolvin~ and dislodging the obstruction
16 using solvents.
17 What is claimed is:
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