CA2152002C

CA2152002C - Nebulizing catheter system and methods of use and manufacture

Info

Publication number: CA2152002C
Application number: CA002152002A
Authority: CA
Inventors: George Baran
Original assignee: Trudell Medical Ltd
Current assignee: Trudell Medical Ltd
Priority date: 1994-06-17
Filing date: 1995-06-16
Publication date: 2009-01-27
Anticipated expiration: 2015-06-16
Also published as: BR9502836A; US20090107503A1; AU700225B2; DE69532843T2; IL114154A0; EP1433493A2; KR960000256A; RU2141351C1; DE69532843D1; EP1433493B1; JPH0838607A; AU2169995A; US5964223A; EP0692273A1; ATE263595T1; ZA954936B; US6526976B1; ATE527009T1; JP3869412B2; CA2152002A1

Abstract

A method and apparatus for delivering a medicine to a patient via the patient's respiratory system with control and efficiency. A nebulization catheter is positioned in the patient's respiratory system so that a distal end of the nebulization catheter is in the respiratory system and a proximal end is outside the body. In a first aspect, the nebulization catheter may be used in conjunction with an endotracheal tube and preferably is removable from the endotracheal tube. The nebulization catheter conveys medicine in liquid form to the distal end at which location the medicine is nebulized by a pressurized gas or other nebulizing mechanism. The nebulized medicine is conveyed to the patient's lungs by the patient's respiration which may be assisted by a ventilator. By producing the aerosol of the liquid medicine at a location inside the patient's respiratory system, the nebulizing catheter provides for increased efficiency and control of the dosage of medicine being delivered. In further aspects of the nebulizing catheter apparatus and method, alternative tip constructions, flow pulsation patterns, centering devices, sensing devices, and aspiration features afford greater efficiency and control of aerosolized medicine dosage delivery.

Description

NEBULIZING CATHETER SYSTEM AND
METHODS OF USE AND MANUFACTURE
BACKGROUND OF THE INVENTION

The present invention relates to aerosol delivery of medication to the lungs and more particularly, the present invention relates to delivery systems for application of nebulized medication to the lungs with improved delivery rates, efficiencies, and control.

Many types of medication can be administered to a patient via the respiratory tract. Medication delivered through the respiratory tract may be carried with a patient's inhalation breath as airborne particles (e.g. an aerosol or nebula) into the lungs where the medication can cross through the thin membrane of the alveoli and enter the patient's bloodstream. Delivery of medication via the respiratory tract may be preferred in many circumstances because medication delivered this way enters the bloodstream very rapidly. Delivery of medication to the lungs may also be preferred when the medication is used in a treatment of a disease or condition affecting the lungs in order to apply or target the medication as close as physically possible to the diseased area.

Although delivery of medication via the respiratory tract has been used for many years, there are difficulties associated with prior systems that have 1 limited their use and application. For example, 2 conventional methods have provided for only limited 3 medication delivery rates, efficiency, and control.

4 Conventional methods for aerosol delivery result in a substantial portion of the medicine failing to be 6 delivered to the lungs, and thereby possibly being 7 wasted, or possibly being delivered to other parts of the 8 body, e.g. the trachea.
9 Aerosols in general are relatively short-lived and can settle out into larger particles or droplets 11 relatively quickly. Aerosols can also impact each other 12 or other objects, settle out as sediment, diffuse, or 13 coalesce. Aerosol particles can also be subject to 14 hydroscopic growth as they travel. Delivery of medicine as airborne particles requires conversion of the 16 medicine, which may be in liquid form, to an aerosol 17 followed relatively quickly by application of the aerosol 18 to the respiratory tract. One such device that has been 19 utilized for this purpose is an inhaler. Inhalers may atomize a liquid to form an aerosol which a person 21 inhales via the mouth or nose. Inhalers typically 22 provide only limited delivery of medication to the lungs 23 since most of the medication is deposited on the linings 24 of the respiratory tract. It is estimated that as little as 10-15% of an aerosol inhaled in this way reaches the 26 alveoli.
27 Aerosol delivery of a medication to a patient's 28 respiratory tract also may be performed while the patient 29 is intubated, i.e. when an endotracheal tube is positioned in the patient's trachea to assist in 31 breathing. When an endotracheal tube is positioned in a 32 patient, a proximal end of the endotracheal tube may be 33 connected to a mechanical ventilator and the distal end 34 is located in the trachea. An aerosol may be added to the airflow in the ventilator circuit of the endotracheal 36 tube and carried by the patient's inhalation to the 37 lungs. A significant amount of the aerosolized 1 medication may be deposited inside the endotracheal tube 2 and the delivery rate of the medicine to the lungs also 3 remains relatively low and unpredictable.
4 The low and unpredictable delivery rates of prior aerosol delivery systems have limited the types of 6 medications that are delivered via the respiratory tract.
7 For new medications that are relatively expensive, the 8 amount of wasted medicine may be a significant cost 9 factor in the price of the therapy. Therefore, it would be advantageous to increase the delivery rate or 11 efficiency of a medicine delivered to the lungs.
12 Another consideration is that some aerosols 13 delivered to the lungs may have adverse side effects, 14 e.g. radioactive tracers used for lung scans. Therefore, it would be advantageous to minimize the overall amount 16 of medication delivered while maintaining the efficacy of 17 the medication by providing the same or a greater amount 18 of the medication to the desired site in the respiratory 19 tract.
Further, some medications may be more effective 21 when delivered in certain particle sizes. Accordingly, 22 an improved aerosol delivery system may provide for 23 improved rates and efficiencies of delivery also taking 24 into account the aerosol particle size.
It may also be important to administer certain 26 medications in specific, controlled dosages. The prior 27 methods of aerosol delivery not only were inefficient, 28 but also did not provide a reliable means to control 29 precisely the dosage being delivered.
It may also be advantageous to be able to 31 target medication to a specific bronchus, or specific 32 groups of bronchia, as desired, while avoiding delivery 33 of inedication to other portions of the lungs.
34 Taking into account these and other considerations, aerosol delivery via the respiratory 36 tract could become an even more widely used and effective 65:102-72 means of medication delivery if the delivery rate and efficiency of the delivery could be improved.

SUMMARY OF THE INVENTION

A method and apparatus are disclosed for delivering a drug with control and efficiency to a patient via the patient's respiratory system. A nebulization catheter is positioned in the patient's respiratory system so that a distal end of the nebulization catheter is in the respiratory system and a proximal end is outside the body.
According to a first aspect, the nebulization catheter may be used in conjunction with an endotracheal tube and preferably is removable from the endotracheal tube. The nebulization catheter conveys medicine in liquid form to the distal end at which location the medicine is nebulized by a pressurized gas or other nebulizing agent. The nebulized medicine is conveyed to the patient's lungs by the patient's respiration which may be assisted by a ventilator. The nebulizing catheter incorporates alternative constructions taking into account anatomical considerations and the properties of the medicine being nebulized to provide delivery of medicine with control and efficiency.
According to one aspect the invention provides a catheter for delivering an aerosol of medicine to a patient comprising: a catheter shaft having a proximal end and a distal end; a lumen through the catheter shaft and communicating at the proximal end with a port for receiving a medicine in a liquid form and communicating at the distal end with a distal orifice from which the medicine can be discharged; means for nebulizing the medicine discharged at the distal orifice into an aerosol plume of particles of the medicine; and means for modifying the aerosol plume of particles of medicine, wherein the modifying means comprises -4a-a vacuum orifice located close to the distal orifice from which the medicine is discharged for scavenging air from the nebulized aerosol.

According to another aspect the invention provides a catheter system for delivering an aerosol of medicine to a patient comprising: a catheter shaft having a proximal end and a distal end; a lumen through the catheter shaft and communicating at the proximal end with a port for receiving a medicine in a liquid form and communicating at the distal end with a distal orifice from which the medicine can be discharged; means for nebulizing the medicine discharged at the distal orifice; and a flow control apparatus connected to the port, said flow control apparatus comprising: a flow line communicating with the port, said flow line occupied by the medicine; a valve associated with the flow line to cause pulsed delivery of medicine through the flow line; and a draw back area associated with the flow line, said draw back area adapted to cause a reversal of flow of medicine through the flow line controller synchronized with the pulsed delivery.

According to another aspect the invention provides a catheter for delivering an aerosol to a patient comprising: a shaft comprised of: an outer tubular member defining a first lumen and terminating at a distal end in a first distal orifice; an inner tubular member defining a second lumen, said inner tubular member located in the first lumen and terminating at a distal end in a second distal orifice; a manifold connected to a proximal portion of said shaft, said manifold having: a first port communicating with the first lumen for conveyance of a pressurized gas in an annular region between the inner and outer tubular members; and a second port communicating with the second lumen for conveyance of a medicine; said second distal ,. ,., -4b-orifice aligned with said first distal orifice to nebulize the medicine from a distal tip of the catheter; and a retractable pin located in said second lumen.

According to another aspect the invention provides a catheter system for delivering an aerosol therapy to a patient comprising: a stand-alone nebulization catheter having a distal end for insertion into the patient and a proximal end, said nebulization catheter having: a catheter shaft; a gas pressurization lumen extending through said catheter shaft; a distal gas exit orifice communicating with said gas pressurization lumen, said distal gas exit orifice located at the distal end of said nebulization catheter; a drug delivery lumen extending along at least a portion of said catheter shaft; a distal drug delivery orifice communicating with said drug delivery channel, said distal drug delivery orifice located in proximity to the distal gas exit orifice so that gas exiting from said distal gas exit orifice nebulizes a drug delivered from said distal drug delivery orifice; and a centering apparatus located on said catheter shaft close to the distal end.

According to another aspect the invention provides a catheter system for delivering an aerosol therapy to a patient comprising: a stand-alone nebulization catheter having a distal end for insertion into the patient and a proximal end, said nebulization catheter having: a catheter shaft; a gas pressurization lumen extending through said catheter shaft; a distal gas exit orifice communicating with said gas pressurization lumen, said distal gas exit orifice located at the distal end of said nebulization catheter; a drug delivery lumen extending along at least a portion of said catheter shaft; a distal drug delivery orifice communicating with said drug delivery channel, said distal drug delivery orifice located in proximity to the distal gas -4c-exit orifice so that gas exiting from said distal gas exit orifice nebulizes a drug delivered from said distal drug delivery orifice; and a valve located in at least one of the lumens.

According to another aspect the invention provides a catheter system for delivering an aerosol therapy to a patient comprising: a stand-alone nebulization catheter having a distal end for insertion into the patient and a proximal end, said nebulization catheter having: a catheter shaft; a gas pressurization lumen extending through said catheter shaft; a distal gas exit orifice communicating with said gas pressurization lumen, said distal gas exit orifice located at the distal end of said nebulization catheter; a drug delivery lumen extending along at least a portion of said catheter shaft; a distal drug delivery orifice communicating with said drug delivery channel, said distal drug delivery orifice located in proximity to the distal gas exit orifice so that gas exiting from said distal gas exit orifice nebulizes a drug delivered from said distal drug delivery orifice; and a retractable pin located in at least one of said lumens.

According to another aspect the invention provides catheter system for delivering an aerosol therapy to a patient comprising: a stand-alone nebulization catheter having a distal end for insertion into the patient and a proximal end, said nebulization catheter having: a catheter shaft; a gas pressurization lumen extending through said catheter shaft; a distal gas exit orifice communicating with said gas pressurization lumen, said distal gas exit orifice located at the distal end of said nebulization catheter; a drug delivery lumen extending along at least a portion of said catheter shaft; a distal drug delivery orifice communicating with said drug delivery channel, said distal 659.02-72 -4d-drug delivery orifice located in proximity to the distal gas exit orifice so that gas exiting from said distal gas exit orifice nebulizes a drug delivered from said distal drug delivery orifice; and a baffle located at the distal end of the nebulization catheter in front of the orifices.
According to another aspect the invention provides a catheter system for delivering an aerosol therapy to a patient comprising: a stand-alone nebulization catheter having a distal end for insertion into the patient and a proximal end, said nebulization catheter having: a catheter shaft; a gas pressurization lumen extending through said catheter shaft; a distal gas exit orifice communicating with said gas pressurization lumen, said distal gas exit orifice located at the distal end of said nebulization catheter; a drug delivery lumen extending along at least a portion of said catheter shaft; a distal drug delivery orifice communicating with said drug delivery channel, said distal drug delivery orifice located in proximity to the distal gas exit orifice so that gas exiting from said distal gas exit orifice nebulizes a drug delivered from said distal drug delivery orifice; and wherein said catheter shaft includes a third lumen extending therethrough and a fiber optic scope extending through said third lumen.

According to another aspect the invention provides a catheter system for delivering an aerosol therapy to a patient comprising: a stand-alone nebulization catheter having a distal end for insertion into the patient and a proximal end, said nebulization catheter having: a catheter shaft; a gas pressurization lumen extending through said catheter shaft; a distal gas exit orifice communicating with said gas pressurization lumen, said distal gas exit orifice located at the distal end of said nebulization catheter; a drug delivery lumen extending along at least a portion of -4e-said catheter shaft; a distal drug delivery orifice communicating with said drug delivery channel, said distal drug delivery orifice located in proximity to the distal gas exit orifice so that gas exiting from said distal gas exit orifice nebulizes a drug delivered from said distal drug delivery orifice; and wherein at least a portion of said shaft surrounding said drug delivery lumen is formed of a low compliance material so that flow control at said distal drug delivery orifice of a fluid delivered through said drug delivery lumen is more responsive to flow control at a location proximal thereto.

According to another aspect the invention provides a catheter system for delivering an aerosol therapy to a patient comprising: a stand-alone nebulization catheter having a distal end for insertion into the patient and a proximal end, said nebulization catheter having: a catheter shaft; a gas pressurization lumen extending through said catheter shaft; a distal gas exit orifice communicating with said gas pressurization lumen, said distal gas exit orifice located at the distal end of said nebulization catheter; a drug delivery lumen extending along at least a portion of said catheter shaft; a distal drug delivery orifice communicating with said drug delivery channel, said distal drug delivery orifice located in proximity to the distal gas exit orifice so that gas exiting from said distal gas exit orifice nebulizes a drug delivered from said distal drug delivery orifice; and a vibrating material located close to said distal orifices.

According to another aspect the invention provides a catheter system for delivering an aerosol therapy to a patient comprising: a stand-alone nebulization catheter having a distal end for insertion into the patient and a proximal end, said nebulization catheter having: a catheter -4f-shaft; a gas pressurization lumen extending through said catheter shaft; a distal gas exit orifice communicating with said gas pressurization lumen, said distal gas exit orifice located at the distal end of said nebulization catheter; a drug delivery lumen extending along at least a portion of said catheter shaft; a distal drug delivery orifice communicating with said drug delivery channel, said distal drug delivery orifice located in proximity to the distal gas exit orifice so that gas exiting from said distal gas exit orifice nebulizes a drug delivered from said distal drug delivery orifice wherein the distal gas orifice comprises a distal plug disposed at the distal end of the catheter shaft, the distal plug comprising a plurality of apertures, and wherein the apertures define gas orifices in communication with the gas lumen.

According to another aspect the invention provides a catheter for delivering an aerosol of medicine to a patient comprising: a catheter shaft; a liquid lumen centrally located in said shaft and adapted for conveying a medicine in liquid form; a plurality of gas lumens peripherally located around said liquid lumen and adapted for conveying a gas; a distal liquid orifice communicating with said liquid lumen; and a plurality of distal gas orifices communicating with said plurality of gas lumens, said plurality of distal gas orifices being aligned with respect to said distal liquid orifice so as to nebulize a liquid medicine discharged from the liquid orifice.

According to another aspect the invention provides a catheter system comprising: a catheter shaft having: a liquid lumen centrally located in said shaft and adapted for conveying a medicine in liquid form; a plurality of gas lumens peripherally located around said liquid lumen and adapted for conveying a gas; a distal liquid orifice -4g-communicating with said liquid lumen; a plurality of distal gas orifices communicating with said plurality of gas lumens, said plurality of distal gas orifices being aligned with respect to said distal liquid orifice so as to nebulize a liquid medicine discharged from the liquid orifice;
wherein the catheter shaft has a proximal end and a distal end and the liquid lumen communicates at the proximal end with a port for receiving a medicine in a liquid form; and a flow control apparatus connected to the port, said flow control apparatus comprising: a flow line communicating with the port, said flow line occupied by the medicine; and a valve associated with the flow line to cause pulsed delivery of medicine through the flow line.

According to another aspect the invention provides a method of forming a catheter for nebulizing a liquid with a gas, the catheter having closely spaced distal orifices comprising: providing a multilumen extruded polymer tubing;
heating a portion of the tubing to a transition temperature of the tubing; forming a j-shaped distal section in the multilumen extruded polymer tubing, wherein the multilumen extruded polymer tubing curves away from a longitudinal axis of the catheter at a distal end of the catheter; and forming a plurality of orifices at the distal section, the plurality of orifices being sized to nebulize a liquid delivered through one of the lumens to form an aerosol with a gas delivered through another of the lumens.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an exploded view of a first embodiment of the present invention.

FIG. 2 shows an assembled view of the embodiment of FIG. 1.

-4h-FIG. 2A is a sectional view of the nebulization catheter of FIGS. 1 and 2.

FIG. 3 is a plan view of an alternative embodiment of the endotracheal tube shown in FIGS. 1 and 2.

1 FIG. 4 is a cross sectional view taken along 2 the line a-a' of the alternative embodiment of the 3 endotracheal tube shown in FIG. 3 without the nebulizing 4 catheter in place.
FIG. 5 is a cross sectional view taken along 6 the line b-b' of the alternative embodiment of the 7 endotracheal tube shown in FIG. 3 with the nebulizing 8 catheter in place.

9 FIG. 6 is a plan view of an embodiment of the nebulizing catheter of FIGS. 1 and 2 shown in place in 11 the trachea of a patient who is not intubated.
12 FIG. 7 is a view similar to that of FIG. 6 13 showing an alternative embodiment of the nebulization 14 catheter.
FIG. 8 is a cross section taken along lines 16 a-a' of the nebulization catheter of FIG. 7.
17 FIG. 9 is a view similar to that of FIG. 7 18 showing an alternative embodiment of the nebulizing 19 catheter shown in FIG. 7.
FIG. 10 is a perspective view of a distal end 21 of an alternative embodiment of the nebulization catheter 22 shown in FIG. 1.
23 FIG. 11 is a perspective view of a distal end 24 of an alternative embodiment of the nebulization catheter shown in FIG. 1.
26 FIG. 12 is a perspective view of an alternative 27 embodiment of FIG. 11 with the liquid lumen shown in a 28 closed condition.
29 FIG. 13 is a perspective view of the embodiment of FIG. 12 with the liquid lumen shown in an open 31 condition.
32 FIG. 14 is a perspective view of a distal end 33 of an alternative embodiment of the nebulization catheter 34 shown in FIG. 1.
FIG. 15 is a perspective view of a distal end 36 of an alternative embodiment of the nebulization catheter 37 shown in FIG. 1.

1 FIG. 16 is a perspective view of a distal end 2 of an alternative embodiment of the nebulization catheter 3 shown in FIG. 1.
4 FIG. 17 is a perspective view of a distal end of an alternative embodiment of the nebulization catheter 6 shown in FIG. 10.
7 FIG. 18 is a perspective view of a distal end 8 of an alternative embodiment of the nebulization catheter 9 shown in FIG. 1.
FIG. 19 is a sectional view of the distal end 11 of the embodiment of the nebulization catheter shown in 12 FIG. 18.
13 FIG. 20 is a sectional view of a distal end of 14 an alternative embodiment of the nebulization catheter shown in FIG. 1.
16 FIG. 21 is a sectional view similar to that of 17 FIG. 20 showing an alternative embodiment of the 18 nebulization catheter shown in FIG. 20.
19 FIG. 22 is a perspective view partially in section of a distal end of an alternative embodiment of 21 the nebulization catheter shown in FIG. 1.
22 FIG. 23 is a view similar to that of FIG. 22, 23 showing an alternative embodiment of the nebulization 24 catheter shown in FIG. 22.
FIG. 24 is a perspective view partially in 26 section of a distal end of an alternative embodiment of 27 the nebulization catheter shown in FIG. 1.
28 FIG. 25 is sectional view of a distal end of an 29 alternative embodiment of the nebulization catheter shown in FIG. 25.
31 FIG. 26 is sectional view similar to that of 32 FIG. 25 showing the embodiment of FIG. 25 during an 33 exhalation stage of the patient.
34 FIG. 27 is a perspective view of alternative embodiments of the nebulization catheter and endotracheal 36 tube shown in FIG. 1.

1 FIG. 28 is a perspective view of alternative 2 embodiments of the nebulization catheter and endotracheal 3 tube shown in FIG. 27.
4 FIG. 29 is a perspective view of an alternative embodiment of the nebulization catheter shown in FIGS. 27 6 and 28.
7 FIG. 30 is a perspective view of the embodiment 8 of the nebulization catheter shown in FIG. 29 shown with 9 an endotracheal tube in a patient's trachea.
FIG. 31 is sectional view of a distal end and a 11 diagrammatic view of a proximal end of an alternative 12 embodiment of the nebulization catheter shown in FIG. 1.
13 FIG. 32 is a cross section view of the 14 embodiment of the nebulization catheter shown in FIG. 31 taken along the line a-a'.
16 FIG. 33 is sectional view of a distal end of an 17 alternative embodiment of the nebulization catheter shown 18 in FIG. 1.
19 FIG. 34 is sectional perspective view of a distal end of an alternative embodiment of the 21 nebulization catheter and endotracheal tube shown in 22 FIG. 2.
23 FIG. 35 is sectional view of a distal end of an 24 alternative embodiment of the nebulization catheter shown in FIG. 1.
26 FIG. 37 is a cross section view of the 27 embodiment of the nebulization catheter shown in FIG. 36 28 taken along the line a-a'.
29 FIG. 38 is a perspective view of a distal end of an alternative embodiment of the nebulization catheter 31 shown in FIGS. 36 and 37.
32 FIG. 39 is a perspective view of alternative 33 embodiments of the nebulization catheter and endotracheal 34 tube shown in FIGS. 37 and 38.
FIG. 40 is sectional perspective view of a 36 distal end of an alternative embodiment of the 37 nebulization catheter shown in FIG. 1.

1 FIG. 41 is a perspective view of alternative 2 embodiments of the nebulization catheter and endotracheal 3 tube of FIG. 1 shown in a patient's trachea.
4 FIG. 42 is a side view of an another embodiment of the nebulization catheter of FIG. 1 showing an 6 alternative centering device.
7 FIG. 43 is a side view of an another embodiment 8 of the nebulization catheter of FIG. 1 showing another 9 alternative centering device.
FIG. 44 is a side view of an another embodiment 11 of the nebulization catheter of FIG. 1 showing yet 12 another alternative centering device.
13 FIG. 45 is a side view of the embodiment of 14 FIG. 44 shown in another stage of operation.

FIG. 46 is a side view of a distal end of a 16 nebulization catheter positioned in a patient's trachea 17 illustrating an undesirable condition.
18 FIG. 47 is a perspective view similar to that 19 of FIG. 40 of alternative embodiments of the nebulization catheter and endotracheal addressing the condition shown 21 in FIG. 46.
22 FIG. 48 shows an alternative embodiment of the 23 nebulizing catheter and endotracheal tube of FIG. 47 24 positioned in a patient's trachea.
FIG. 49 shows an alternative embodiment of the 26 nebulizing catheter of FIG. 6.
27 FIG. 50 is a diagram illustrating an embodiment 28 of a drug reservoir and pressurization assembly that can 29 be utilized in connection with the embodiment of the nebulization catheter of FIG. 1.
31 FIG. 51 is a diagram similar to that of FIG. 50 32 illustrating an alternative embodiment of the drug 33 reservoir and pressurization assembly.
34 FIG. 52 is a sectional view along line c-c' of FIG. 51.

1 FIG. 53 is a side view of an alternative 2 embodiment of FIG. 1 including an optional humidification 3 and heating arrangement.
4 FIG. 54 is a side view of a flow control system used in connection with the embodiment of FIG. 1 used for 6 pressuring the liquid flow lumen.
7 FIG. 55 is a view similar to that of FIG. 54 8 showing the flow control system of FIG. 54 in another 9 stage of operation.
FIG. 56 is a perspective view of an alternative 11 embodiment of the present invention illustrating an 12 alternative method of use.
13 FIG. 57 is a perspective view illustrating an 14 entire nebulization catheter system including sensors.
FIG. 58 shows a sectional view of an embodiment 16 of a nebulizing catheter including a sensor.
17 FIG. 59 shows an alternative embodiment of the 18 nebulizing catheter shown in FIG. 58.
19 FIG. 60 is a sectional view of a distal end of an alternative embodiment of the nebulizing catheter of 21 FIG. 1.
22 FIG. 61 is a sectional view of an embodiment of 23 the present invention that incorporates a baffle to 24 generate a secondary aerosol.
FIG. 62 is a sectional view of another 26 embodiment of the present invention that incorporates a 27 baffle to generate a secondary aerosol.
28 FIG. 63 is a sectional view of yet another 29 embodiment of the present invention that incorporates a baffle to generate a secondary aerosol.
31 FIG. 64 is a sectional view of still another 32 embodiment of the present invention that incorporates a 33 baffle to generate a secondary aerosol.
34 FIG. 65 is a diagram illustrating an embodiment of the present invention that incorporates a pressurized 36 drug/propellant mixture canister.

1 FIG. 66 is a side view of an embodiment of a 2 nebulizing catheter incorporated into of a suction 3 catheter.
4 FIG. 67 is a detailed sectional view of the tip portion of the suction catheter - nebulizing catheter 6 embodiment of FIG. 66.
7 FIG. 68 is a perspective view of the embodiment 8 of FIG. 66 positioned in an endotracheal tube in a 9 patient's respiratory system.
FIG. 69 is cross sectional view of the 11 embodiment of FIG. 66 taken along lines a-a'.

12 FIG. 70 is a perspective view similar to FIG.

13 68 showing the suction catheter advanced during an 14 further stage of operation.
FIG. 71 is a side view of a proximal end of an 16 endotracheal tube illustrating an arrangement of 17 receiving a suction catheter and a nebulization catheter 18 into the endotracheal tube.
19 FIG. 72 is an alternative embodiment of the arrangement shown in FIG. 71.
21 FIG. 73 is another alternative embodiment of 22 the arrangement shown in FIG. 71.
23 FIG. 74 is another embodiment of a suction 24 catheter incorporating aerosol delivery by nebulization.
FIG. 75 is still another embodiment of a 26 suction catheter incorporating aerosol delivery by 27 nebulization.
28 FIG. 76 is a sectional view of a distal end of 29 an embodiment of a nebulizing catheter also incorporating a vibrating tip.
31 FIG. 77 is a sectional view of another 32 embodiment of the nebulizing catheter incorporating 33 micropulsation of the liquid supply.

EMBODIMENTS

The present invention provides for the controlled and efficient delivery of an aerosolized medication to the lungs of a patient by nebulization of a medication at a distal end of a catheter positioned in the respiratory tract. Throughout this specification and these claims, the nebulization catheter is described as used for the delivery of medicine or medication. It is intended that the terms "medication", "medicine", and "drug" should be understood to include other agents that can be delivered to the lungs for diagnostic or therapeutic purposes, such as tracers, or for humidification.

I. Nebulizing Catheter - Basic Configuration Referring to FIGS. 1 and 2, there is depicted a first embodiment of the present invention. FIGS. 1 and 2 show an endotracheal tube 10 which may be a conventional endotracheal tube. The endotracheal tube 10 may have an inflatable cuff 12 located close to its distal end to facilitate positioning the tube 10 in the patient's trachea, or alternatively the endotracheal tube 10 may be of a type without an inflatable cuff. The inflatable cuff 12 is connected via a separate inflation lumen in the endotracheal tube 10 to a proximal fitting 13 for connection to a source of inflating gas (not shown). The endotracheal tube 10 has a proximal end connected to a manifold fitting 14. The fitting 14 has a port 15 suitably adapted for connection to a ventilator circuit (not shown). The fitting 14 also includes another port 16 that permits the introduction of a separate catheter into the endotracheal tube from the proximal end. The fitting 14 may be similar in construction to the elbow fitting described in U.S. Pat. No. 5,078,131 (Foley). In FIG. 1, a nebulizing catheter 20 is located in a position ready to be inserted into a ventilation lumen 22 of the endotracheal tube 10 via the 1 proximal fitting 14. In FIG. 2, the nebulizing catheter 2 20 is positioned fu'Liy in the endotracheal tube 10 with a 3 proximal end extending out of the port 16 of the proximal 4 fitting 14.
At a proximal end of the nebulizing catheter 20 6 is a manifold 24. The manifold 24 includes at least a 7 gas port 28 and a liquid (medicine) port 32. These ports 8 28 and 32 may include conventional attaching means, such 9 as luer lock type fittings. In addition, these ports 28 and 32 may also include closure caps 31 that may be used 11 to close the ports when not in use and may be popped open 12 when connection to a gas source or a liquid source is 13 desired. Optionally, the manifold 24 may also include a 14 filter located in-line with either the gas port 28 or the liquid port 32 or both ports to prevent lumen blockages 16 by particulate matter. The nebulization catheter 20 17 includes at least two separate lumens (as shown in FIG.
18 2A). A first lumen 33 is used for conveyance of a liquid 19 medicine and communicates with the port 32 on the manifold 24. The other lumen 34 is used for conveyance 21 of a pressurized gas and communicates with the port 28 on 22 the manifold 24. The liquid lumen 33 communicates with a 23 distal liquid orifice 35 and the gas lumen 34 24 communicates with a distal gas orifice 36 near a distal end 37 of the nebulization catheter 20. The distal 26 opening 36 of the pressurized gas lumen 34 directs 27 pressurized gas across the distal liquid lumen opening 35 28 thereby nebulizing the liquid medication so that it can 29 be delivered to the patient's lungs. The distal liquid orifice 35 may be open or may be provided with a porous 31 material plug or a sponge-like or felt-like material plug 32 which may extend slightly from the distal orifice and 33 that allows liquid to flow from the orifice yet reduces 34 the likelihood of liquid drooling from the tip.
The length of the nebulization catheter 20 36 should be sufficient so that the distal end 37 can be 37 located in the desired location in the respiratory system 1 while the proximal end (i.e., including the manifold 24) 2 is accessible to the physician or other medical personnel 3 for connection to suitable gas and liquid supplies 4 external of the patient's body. Accordingly, the length of the nebulization catheter is dependant upon the size 6 of the patient in which it is being used. A shorter 7 nebulization catheter may be preferred in smaller 8 patients, such as infants or children, and a longer 9 nebulization catheter may be needed for adults. For example, a nebulization catheter suitable for adults may 11 have a length of approximately 45 cm. In one embodiment, 12 approximately 30 cm of the nebulizing catheter 20 is in 13 the endotracheal tube 10. The nebulization catheter may 14 be introduced into the respiratory system through a patient's mouth or via a tracheostomy tube or through the 16 nasal passages. The nebulization catheter may also be 17 used to deliver an aerosol to a patient's nasal passages 18 in which case the length may be correspondingly shorter.
19 As explained in more detail below, the generation of an aerosol plume with the desired geometry, 21 particle size, velocity, etc., requires that the distal 22 gas and liquid orifices have small dimensions. Also as 23 explained below, the distal gas orifice 36 and the distal 24 liquid orifice 35 should be in close proximity to each other in order to produce an aerosol with the desired 26 characteristics and efficiency. Further, in order to 27 provide the desired medicine,delivery rates and to 28 operate with reasonably available pressure sources, the 29 liquid and gas lumens in the nebulizing catheter should be as large as possible, consistent with anatomical 31 requirements. Accordingly, the nebulization catheter 20 32 has a multiple stage construction with a larger shaft 33 size and larger lumens in a main shaft section and a 34 smaller shaft size and smaller lumens in a distal shaft section.
36 As shown in FIG. 2A, the nebulizing catheter 20 37 is composed of a shaft 38 having a main section 39 and a 1 distal section 40. In the main shaft section 39 of the 2 nebulization catheter, the liquid and gas lumens 33 and 3 34 have a larger size than in the distal shaft section 4 40. For example, in the main shaft section 39, the liquid and gas lumens each may have an I.D. of 6 approximately .010 to .030 inches. At a most proximal 7 end where the main shaft section 39 connects to the 8 manifold 24, the lumens may be even larger. In the 9 distal shaft section 40, the liquid and gas lumens taper to a much smaller I.D. with the liquid lumen 11 approximately .002 to .008 inches or even smaller and the 12 gas lumen .002 to .020 inches. In a preferred 13 embodiment, the liquid and gas orifices 35 and 36 are 14 less than .125 inches apart, and more preferably less than .030 inches apart, and in a most preferred 16 embodiment less than .001 inches apart. In a nebulizing 17 catheter having an overall length of 45 cm, the main 18 shaft section 39 may be approximately 25 cm and the 19 distal shaft section 40 may be approximately 20 cm.
Also, although the liquid and gas lumens are shown to be 21 side by side in FIG. 2A, they may also be constructed to 22 have an coaxial or other arrangement. Further, although 23 the main shaft section 39 is shown to be of a uniform 24 diameter and profile, alternatively it may also have a tapered diameter and profile such that the entire shaft 26 38-is tapered along its length.
27 In a first preferred embodiment of the 28 invention, as shown in FIGS. 1 and 2, the nebulizing 29 catheter 20 is removable, and replaceable with respect to the endotracheal tube 10. This provides several 31 significant advantages. First, the nebulizing catheter 32 20 may be specifically adapted and chosen to have the 33 desired operating characteristics suitable for delivery 34 of the particular medication being administered to the patient. In addition, the fact that the nebulizing tube 36 20 is removable and replaceable provides versatility and 37 flexibility regarding the therapy and dosage regime that 1 can be chosen by the physician. For example, a decision 2 by the physician whether to deliver a medication to the 3 respiratory tract, and the selection of the type and 4 dosage of the medication to be delivered, need not be made by the physician until after the endotracheal tube 6 is already in place in the patient. When the physician 7 determines the proper type of medication to the delivered 8 to the patient via the respiratory tract, the appropriate 9 nebulization catheter can be selected and inserted into the endotracheal tube. Further, the nebulizing catheter 11 20 can be removed after it is used and therefore it is 12 not necessary for the nebulization catheter to be left in 13 the patient and occupy space in the patient's respiratory 14 tract or in the endotracheal tube 10 when it is no longer needed. In addition, the decision regarding the proper 16 type of medication can be revisited again at any time 17 after the endotracheal tube is in place. If a different 18 type of nebulizing catheter is required, such as for 19 sterility purposes, the endotracheal tube need not be replaced as well.
21 Another advantage of providing the nebulization 22 catheter as a separate, removable device is that it can 23 be accommodated in a variety of other instruments and/or 24 devices. For example, the nebulization catheter of FIGS.
1 - 5 is shown used in an endotracheal tube; however, the 26 nebulization catheter could also be positioned inside of 27 a bronchoscope, such as in a working channel of a 28 bronchoscope. The nebulizing catheter could be 29 positioned in any instrument that is positioned in the respiratory tract and that can accommodate the nebulizing 31 catheter size.
32 The nebulizing catheter may be provided with 33 radiopaque markings 41 to facilitate positioning and 34 placement. The radiopaque markings 41 may be provided by radiopaque bands of metal or heat shrunk bands of doped 36 radiopaque plastic that are attached to the nebulizing 37 catheter, or alternatively the markings may be provided 1 by doping the plastic material of the nebulizing catheter 2 with a radiopaque material. Alternatively, a radiopaque 3 dye may be added to the liquid being delivered by the 4 nebulization catheter to assist observation. The markings 41 may be graduated to facilitate recognition, 6 or alternatively may extend over a portion or all of the 7 nebulizing catheter. In still a further embodiment, the 8 markings may be formed of a ultrasonic reflectors, e.g.
9 textured material, that are visible by means of ultrasonic imaging. The nebulization catheter may also 11 include a stripe 43 extending along a side of the shaft 12 (as shown in FIGS. 5 and 6). The stripe 43 may be 13 radiopaque or ultrasonically visible and may be used to 14 determine the rotational orientation of the shaft. The stripe may be formed by a coextrusion process or by 16 embedding a wire in the wall of the nebulization 17 catheter.
18 One method that may be employed to facilitate 19 positioning of the nebulization catheter is to monitor the pressure at the distal end of the endotracheal tube 21 as the nebulization catheter is being advanced.
22 Monitoring the pressure at the end of the endotracheal 23 tube may be accomplished through one of the endotracheal 24 tube lumens. The gas source connected to the proximal end of the nebulization catheter may be operated so as to 26 expel a gas from the distal end of the nebulization 27 catheter as it is being advanced. The gas being expelled 28 from the distal end of the nebulization catheter affects 29 the pressure being detected through the endotracheal tube. When the distal end of the nebulization catheter 31 passes the distal end of the endotracheal tube, the 32 pressure being measured through the endotracheal tube 33 abruptly changes thereby providing a clear indication of 34 the location of the distal end of the nebulization catheter relative to the endotracheal tube.
36 The nebulizing catheter may also include a 37 safety stop 44 located along a proximal portion that 1 engages a portion of the endotracheal tube proximal 2 portion or a fitting thereon, as shown in FIG. 2. The 3 safety stop 44 ensures that the distal end of the 4 nebulizing catheter 20 is correctly positioned with respect to the distal end 46 of the endotracheal tube 10 6 and prevents the distal end 37 of the nebulizing catheter 7 from extending too far into the trachea. In addition to 8 the safety stop 44, the proximal portion of the 9 nebulizing catheter 20 may also have graduated markings 48 that would be visible to the physician handling the 11 proximal end of the nebulizing catheter to enable a 12 determination of the position of the distal end 37 of the 13 nebulizing catheter 20 relative to a distal end 46 of the 14 endotracheal tube 10.
The nebulizing catheter 20 may also include a 16 critical orifice 49 located at a proximal portion of the 17 nebulizing catheter. The critical orifice 49 may be 18 formed by a small critical opening located in line with 19 the gas pressurization lumen 34 of the nebulizing catheter shaft close to the manifold 24. The critical 21 orifice 49 is sized so that if the nebulization catheter 22 is supplied with a flow in excess of its designed 23 operating flow, the critical orifice will allow only the 24 designed operating flow to pass through to the distal gas orifice. Alternatively, a safety valve may be located 26 in the proximal portion of the catheter shaft. The 27 safety valve would be designed to open if supplied with 28 an excess of pressure.
29 In addition, the nebulizing catheter may include a centering device 50. The centering device 50 31 is located close to a distal end of the nebulizing 32 catheter shaft and helps to center and align the distal 33 end of the nebulizing catheter for improved performance, 34 as explained in more detail below.
According to one embodiment, the removable 36 nebulization catheter 20 is enclosed in a storage sheath 37 51. The storage sheath 51 may be similar to the type of 1 storage sheaths used in conjunction with suction 2 catheters. The storage sheath is preferably flexible, 3 collapsible, or extendable to accommodate insertion of 4 the catheter. The storage sheath 51 may be connected to the fitting 14. The storage sheath 51 can be used to 6 receive the nebulizing catheter 20 when it is being 7 withdrawn from the endotracheal tube 10. The storage 8 sheath 51 is sealed and can maintain the withdrawn 9 nebulizing catheter in an isolated condition when it is temporarily removed from the patient's respiratory 11 system. The storage sheath 51 also allows the physician 12 to re-insert the nebulization catheter into the patient.
13 In this manner, the nebulization catheter can be reused 14 in a limited way with respect to a patient and can be maintained in a sterile condition while withdrawn from 16 the patient. The storage sheath 51 may have a distal 17 sleeve 53 that can slide along the shaft of the 18 nebulization catheter so that the nebulization catheter 19 may be advanced into the ventilation lumen of the endotracheal tube or withdrawn into the storage sheath 21 51. The sleeve 53 may have a close fitting seal 55 22 located therein which is designed to clean and/or wash 23 the nebulization catheter when it is withdrawn into the 24 sheath. Alternatively, a cleaning seal 55 may be located in the port 16 of manifold fitting 14.
26 Another feature that may be used in conjunction 27 with certain procedures is radiation shielding. Some 28 procedures for which the nebulization catheter may be 29 used may involve the delivery of radioactive agents, e.g.
tracers to the lungs. To minimize exposure to 31 radioactive materials, the nebulizing catheter may be 32 provided with shielding over all or a significant portion 33 of the overall length of the catheter. Shielding may 34 also be provided at the liquid source reservoir.
The nebulizing catheter is preferably 36 constructed of a biocompatible, chemically resistant 37 polymer in order that it is suitable for use with a wide 1 variety of drugs. The catheter shaft is preferably clear 2 to allow visualization of contaminants or blockages of 3 the interior lumens. Also, the portion of the catheter 4 shaft that forms the liquid lumen 33 is preferably composed of a relatively non-compliant material. In a 6 present embodiment, the catheter shaft is composed of a 7 polymer such as polyethylene or nylon. A polymer tubing 8 is extruded with multiple lumens to be used for the 9 separate gas and liquid lumens. In order to produce a nebulization catheter with the tapered distal section 40, 11 a multi-lumen extruded tubing may be drawn down in a 12 portion thereof to form the tapered distal section 40.
13 The draw down ratio may be selected to provide a 14 nebulization catheter shaft with the desired dimensions.
The draw down process serves to make the lumens smaller 16 in size distally as well as closer together while 17 maintaining the proximal cross sectional profile of the 18 multi-lumen tubing. The larger proximal profile provides 19 for greater pushability in the catheter shaft and facilitates manufacturing by making the manifold 21 connection easier. The draw down ratio used on the 22 extruded polymer tubing may be on the order of 2-to-1, 5-23 to-1, or even as high as 20-to-1 or higher. Prior to 24 drawing down, the extruded polymer tubing is preferably exposed to high energy radiation to crosslink the polymer 26 molecules to provide for favorable material properties, 27 such as the ability to maintain orifice dimensions and 28 tolerances. The radiation may have an energy of 29 approximately 10-700 kgy. After the crosslinking step, the tubing is heated to its transition temperature 31 between its melt and glass states, and is drawn down by 32 the desired ratio.
33 As an alternative to drawing down the extruded 34 tubing, the multi-stage nebulization catheter shaft may be formed by a bubble extrusion process wherein the 36 desired tapered distal section is formed directly in the 37 shaft as it is being extruded. Again, this process may 1 be used for manufacturing efficiency and convenience. As 2 another alternative, the multi-stage shaft may be formed 3 by a combination of both bubble extrusion and drawing 4 down. Still another alternative for forming the desired tapered profile for the nebulizing catheter shaft is to 6 use a.material that can be cold drawn in order to cause a 7 sharp neck down in diameter, such as a linear low density 8 polyethylene. Although the process for forming the 9 tubing is particularly suited for producing a nebulization catheter shaft for use in delivering 11 medicine to the respiratory tract, it should be 12 understood that the process could be used to produce 13 aerosol nozzles for non-medical purposes as well.
14 Alternatively, all or part of the nebulization catheter shaft can be molded, especially at locations 16 where close tolerances are preferred such as at the tip.
17 After the shaft is formed with the desired 18 stages, it is cut and assembled with the other components 19 of the nebulizing catheter. Although the nebulization catheter is preferably constructed of a polymer, in an 21 alternative embodiment it could be formed of other 22 materials such as a metal, especially a malleable metal 23 to facilitate drawing, shaping or forming orifices.

24 During the manufacturing process, the nebulizing catheter may be pre-sterilized by means of a conventional process, 26 such as a gamma ray or electron beam. The nebulizing 27 catheter is preferably disposable after use with a single 28 patient, but may be reused to a limited extent with a 29 single patient provided that contamination can be prevented such as through the use of the sheath 51, 31 described above. The nebulizing catheter shaft 32 preferably possesses torsional rigidity so that rotation 33 of the proximal end is transmitted at a 1:1 ratio to the 34 distal end. The nebulizing catheter may also be provided with an antiseptic coating.
36 Drug delivery rates are closely related to the 37 particle size with larger particles providing greater 1 delivery rates. The embodiments of the nebulization 2 catheter described herein have the capability of 3 generating particle distributions with a GSD between 2 4 and 2.5. Drug delivery rates in a range between approximately 5 and 1000 mg (.005 - 1.0 ml) per minute 6 may be obtained. A variety of particle size 7 distributions can be generated at most flow rates through 8 selection of the catheter type and aerosol volume output.
9 An aerosol of this type can be generated with the nebulization catheter using a gas flow rate as low as 0.1 11 liter/minute.
12 There are a number of factors that affect the 13 particle size generated. These factors include: (1) the 14 gas orifice diameter, (2) the liquid orifice diameter, (3) the liquid delivery tube outer diameter and geometry, 16 (4) the distance between the gas and liquid orifices, (5) 17 the rate of gas delivery, and (6) the pressure of the 18 liquid. Of course, the size of the solid particles in 19 suspension, if present, in the liquid are a defining aspect of the aerosol particle size generated. In 21 addition, there are other factors that affect the aerosol 22 particle size such as the characteristics of the liquid, 23 e.g. viscosity, suspension, surface tension and the 24 composition of the driving gas, however, these factors affect the particle size of the aerosol generated to a 26 lesser degree. By selectively varying these parameters, 27 the size and size distribution of the aerosol particles 28 can be changed from less than a micron to at least 10 29 microns.
The embodiments of the present invention, 31 described herein are suitable for delivery of an aerosol 32 by nebulization with a volumetric particle size 33 distribution comparable to other nebulization systems.
34 Further, by generating an aerosol at a location in the trachea or even deeper in the bronchi, impaction losses 36 in tract can be avoided. By reducing impaction losses, 37 it may be acceptable to use larger particle sizes (e.g.

1 greater than 5 microns). The combination of lower 2 impaction losses and larger particle sizes may provide 3 higher effective delivery rates than prior systems.
4 Reducing impaction losses would enable an embodiment of the nebulization catheter to provide acceptable delivery 6 rates with aerosol particle sizes greater than 5 microns.
7 Referring to FIGS. 3 - 5, there is depicted a 8 further embodiment of the present invention. According 9 to the embodiment of FIGS. 3 - 5, there is provided an endotracheal tube 52 and a nebulizing catheter. The 11 nebulizing catheter may be similar to the nebulizing 12 catheter 20 shown in FIGS. 1 through 3. In the 13 embodiment of FIGS. 3 - 5, the endotracheal tube 52 has 14 an auxiliary lumen 56 in addition to its main ventilation lumen 60. Some endotracheal tubes provide auxiliary 16 lumens through the shaft wall. The auxiliary lumen 56 is 17 preferably sized and adapted to receive the separate 18 nebulization catheter 20. This embodiment provides many 19 of the same advantages as the embodiment of FIGS. 1 through 3. In addition, in this embodiment, the 21 auxiliary lumen 56 may be provided with a distal aperture 22 64 that facilitates locating and aligning the distal end 23 of 37 the nebulizing catheter 20 at a desired location 24 for nebulization purposes.
In the embodiments of the invention shown in 26 FIGS. 1-5, the nebulizing catheter 20 is shown used in 27 conjunction with an endotracheal tube either of a 28 conventional type 10, as in FIGS. 1 and 2, or of a type 29 especially designed for use with the nebulizing catheter such as endotracheal tube 52 of FIGS. 3 - 5. The 31 nebulizing catheter 20 according to an embodiment of the 32 present invention may also be used without a separate 33 endotracheal tube, i.e. the nebulizing catheter may be 34 used on a patient who is not intubated, as shown in FIG.
6. If used on a spontaneously breathing patient (without 36 an endotracheal tube), the patient should be properly 1 anesthetized and/or that the airway passage of the 2 patient be topically anesthetized. The nebulizing 3 catheter 20 is positioned in the respiratory system of a 4 patient directed past the carina 68 into one of the bronchi 72 of the lungs. Alternatively, the nebulizing 6 catheter 20 may also be positioned proximal of the carina 7 in the trachea, as desired. Embodiments of the 8 nebulizing catheter may also be used on patients who have 9 had tracheotomies or who have tracheotomy tubes.
In the embodiment of FIG. 6, a guiding sheath 11 73 is used. The guiding sheath 73 is used to help 12 position the nebulizing catheter 20 in the respiratory 13 system of the patient. The guiding sheath 73 includes a 14 lumen through which the nebulization catheter 20 can be advanced into a desired bronchi site. To facilitate 16 positioning the nebulization catheter, the guiding sheath 17 73 may have a pre-shaped distal end to facilitate 18 locating the sheath in the desired airway passage.
19 Alternatively, the guiding sheath 73 may have a distal end that can be formed into a desired shape by the 21 physician just prior to insertion. The guiding sheath 73 22 differs from the endotracheal tube 10 of FIGS. 1-5 in 23 that it may have a smaller outside diameter so that it 24 can be advanced into smaller airway passages deep in the patient's bronchi past the carina 68. The inside 26 diameter of the sheath 73 is large enough to advance the 27 nebulization catheter. The guiding sheath 73 is 28 particularly useful when the nebulization catheter 20 is 29 being located deep in the patient's'lungs, or when the nebulization catheter is used without an endotracheal 31 tube. The guiding sheath 73 may also be used with an 32 endotracheal tube through the ventilation lumen thereof.
33 The guiding sheath is preferably composed of a 34 torsionally rigid material so that the distal end of the guiding sheath is responsive to rotation at the proximal 36 end.

1 Referring to FIGS. 7 and 8, there is shown 2 another embodiment of the nebulizing catheter. In the 3 embodiment of FIG. 7, a nebulizing catheter 76 includes 4 an occlusion balloon 80 located on a distal exterior surface of the nebulizing catheter shaft body 84. The 6 nebulizing catheter 76 may include an additional lumen 7 88, as shown in FIG. 8, located therethrough and 8 communicating with the interior of the balloon 80 for 9 providing inflation fluid, i.e. preferably gas, to expand the occlusion balloon 80. This lumen 88 for inflation 11 fluid is in addition to the lumens 92 and 96 in the 12 catheter shaft 84 used for conveyance of the liquid 13 medicine and pressurized gas, respectively. The 14 occlusion balloon 80 may be used to position the nebulizing catheter in the appropriate respiratory branch 16 100, center the nebulizing catheter tip for proper 17 orientation, and isolate a particular bronchus, as 18 needed. The embodiment of the nebulizing catheter 76 19 shown in FIG. 7 may be used with an endotracheal tube in a manner similar to that shown in FIGS. 1-3, or 21 alternatively it may be used without a separated 22 endotracheal tube, similar to the embodiment of FIG. 6.
23 When used without a separate endotracheal tube, the 24 nebulizing catheter 76 of FIG. 7 could be used for the purpose of selective ventilation of one of the bronchi of 26 the lungs even without providing aerosolization.
27 Alternatively, the nebulization catheter 76 could provide 28 aerosolization on an intermittent basis with continuous 29 ventilation. If the nebulization catheter is used to provide ventilation as well as aerosolized medication, 31 the ventilation regime can be tailored to maximize 32 aerosol transport.
33 In addition, to further facilitate positioning 34 and placement, the nebulizing catheter 76 may be used with a guide wire 104. The nebulizing catheter may be 36 provided with a separate guide wire lumen 108 to receive 37 the guide wire 104, or alternatively, the guide wire may 1 use one of the existing lumens that is also used for 2 either the pressurized gas or the liquid or alternatively 3 the guide wire may be incorporated and fixed into the 4 nebulizing catheter so that it is non-removable. The guide wire, whether of the removable type of the type 6 that.is fixed to the nebulizing catheter, may also be 7 steerable, i.e. so that it can be guided from a proximal 8 end to access the appropriate location in the lungs. The 9 steering apparatus may utilize selective tensioning of a pull wire, etc. from a proximal end. If the guide wire 11 is of the separate removable type, it may be withdrawn 12 after it has been used to position the distal tip of the 13 nebulizing catheter so as to avoid interfering with 14 aerosol delivery. In addition, the distal tip of the guide wire or nebulization catheter may be pre-shaped or 16 shapable by the physician so as to impart an appropriate 17 curve or bend to facilitate access to the desired airway.
18 Referring to FIG. 9, there is shown another 19 embodiment of a nebulizing catheter of FIG. 7. The embodiment of FIG. 9 is similar to the embodiment of FIG.
21 7 with the exception that the separate guide wire 104 is 22 received in a loop 106 located close to a distal end of 23 the nebulizing catheter 76. Proximal of the loop 106, 24 the guide wire 104 is positioned adjacent to the shaft 84 of the nebulizing catheter 76. Instead of a loop 106, 26 the guide wire may be received in a short lumen located 27 in the distal end of the nebulizing catheter.

28 II. Generation of Aerosol Plume 29 It has been discovered that the shape of the aerosol plume can be a significant factor affecting the 31 rate and efficacy of the delivery of medication by an 32 aerosol. In general, it is preferable to generate an 33 aerosol that has a shape that minimizes particle 34 impaction near the distal tip of the nebulizing catheter, given the location of the tip and the airflow conditions 36 around it. For example, if the aerosol plume is wide, a 1 portion of the drug may be wasted in the end of the 2 endotracheal tube or on the wall of the trachea or other 3 airway passage. On the other hand, if the plume is too 4 narrow or the velocity too high, a portion of the drug may impact excessively on the patient's carina. In 6 general, a low aerosol particle velocity is desirable.
7 One of the reasons for this is to avoid impacting the 8 carina with the discharge of high velocity aerosol 9 particles. In addition, it is also generally desirable to have as wide an aerosol plume as possible while 11 avoiding significant impact with the walls of either the 12 endotracheal tube or the respiratory airway passage. The 13 effects of aerosol plume velocity and geometry are 14 related to anatomical factors. In some circumstances, e.g. away from the carina, a narrow, fast aerosol plume 16 may be preferable to a slower, wider plume.
17 Regarding the embodiments described below, 18 certain of the embodiments may be preferable from the 19 standpoint of versatility, i.e. they may be able to deliver a variety of medications having different 21 viscosities, suspensions, surface tensions, etc. Others 22 of the embodiments may be more suitable for the delivery 23 of specific types of medications or the delivery of 24 particles of certain sizes.
Referring to FIG. 10, there is shown a tip 26 configuration for a nebulizing catheter 112. The 27 nebulizing catheter 112 may be either a stand alone-type 28 of nebulizing catheter, similar to the catheters shown in 29 FIGS. 6 and 10, or may be incorporated into an endotracheal tube either removably, as in FIGS. 1 - 5, or 31 non-removably. In the embodiment of FIG. 10, the 32 nebulizing catheter 112 has a coaxial configuration.
33 Specifically, the nebulizing catheter 112 includes an 34 outer tubular member 116 defining a lumen 120 and an inner tubular member 124 also defining a lumen 128. The 36 inner tubular member 124 is located in the lumen 120 of 37 the outer tubular member 116. According to the 1 embodiment shown FIG. 6, pressurized gas is conveyed in 2 the annular region defined between the inner and outer 3 tubular members. Liquid medication is conveyed in the 4 lumen 128 of the inner member 124. As shown in the embodiment of FIG. 10, a distal end of the outer tubular 6 member 116 is approximately adjacent to a distal,end of 7 the inner tubular member 124. In the embodiment of FIG.
8 10, the outer tubular member 116 has an O.D. of 9 approximately .008 inches and an I.D. of approximately .006 inches. The inner tubular member 124 has an O.D. of 11 approximately .003 inches and I.D. of approximately .0015 12 inches. Both the inner tubular member 124 and the outer 13 tubular member 116 have larger dimensions proximal of the 14 distal tip portion. Along a main shaft portion proximal of the distal tip, the outer tubular member 116 has an 16 O.D. of approximately .115 inches and an I.D. of .080 17 inches and the inner tubular member 124 has an O.D. of 18 approximately .060 inches and an I.D. of .050 inches.
19 The embodiment of FIG. 11 shows a tip of a nebulizing catheter 132. This embodiment is similar to 21 the embodiment of FIG. 10. The tip 133 is formed with a 22 plurality of lumens terminating in a plurality of 23 orifices. An inner lumen 134 is used to convey the 24 liquid medication and the surrounding lumens 135 convey the pressurized gas used to nebulize the liquid. This 26 embodiment has the advantage that the orifice of the 27 liquid lumen 134 is centered with a fixed spacing 28 relative to the orifices of the gas lumens 135 around it.
29 In the embodiment of FIG. 11, the multiple lumen construction may extend all the way back to the proximal 31 end of the nebulizing catheter 132 or alternatively, only 32 a distal segment may have the multiple gas lumen 33 configuration in which case the pressurized gas may be 34 conveyed through a single proximal lumen that connects to the multiple distal lumens.

2j52fl02 1 FIGS. 12 and 13 show an alternative embodiment 2 136 of the multiple lumen nebulization catheter in FIG.
3 11. The embodiment in FIGS. 12 and 13 is useful when it 4 is desired to provide the aerosol medicine with a pulsed delivery. The pulsed delivery may be timed to coincide 6 with the inhalation of the patient so that aerosol is not 7 wasted when the patient is exhaling. A potential 8 drawback with pulsed delivery is that the aerosol may 9 drool from the tip of the nebulizing catheter when the pressure being applied to the liquid is reduced to effect 11 the pulsation. To avoid this potential problem, the 12 nebulizing catheter 136 provides for closure of the 13 liquid lumen when the pressure being applied to it is 14 reduced. As in the previously described embodiment, the nebulization catheter 136 in FIGS. 13 and 14, has a 16 centrally located lumen 137 for delivery of a liquid 17 medicine and a plurality of lumens 138 surrounding the 18 central lumen 137 for conveyance of a pressurized gas to 19 nebulize the liquid at the distal orifice 139. In this embodiment, the catheter 137 is formed of a low 21 compliance material in the outer wall area 140 and a 22 relatively high compliance material in the area 141 23 surrounding the centrally located liquid lumen 137.
24 These differing compliance characteristics may be formed in the catheter shaft by coextruding a single tube with 26 different materials. When using the embodiment of FIGS.
27 12 and 13, a constant, relatively high pressure is 28 applied to the gas in the lumens 138. Liquid medicine is 29 delivered via the lumen 137 and pressure pulses are applied to the liquid from an external delivery source, 31 such as a pump. When the pressure in the liquid lumen 32 137 is low, the high pressure in the gas lumens 138 33 deform the compliant inner material 141 thereby 34 compressing the liquid lumen 137 and closing it off, as shown in FIG. 12. When a pressure pulse is applied to 36 the liquid in the lumen 137, it overcomes the compressive 37 forces from the gas lumens 138 allowing the lumen 137 to 1 open and permitting the liquid medicine to be delivered 2 to the distal orifice 139 to be nebulized, as shown in 3 FIG. 13. In this manner, the embodiment of FIGS. 12 and 4 13 provides for pulsed liquid nebulization with reduced possibility of drooling.
6 Another feature shown in FIGS. 11 and 12 is a 7 porous plug 142 located in the liquid orifice 139. This 8 porous plug may be made of a felt-like material and may 9 assist in the production of fine aerosol particles.

The embodiment of FIG. 14 shows a distal tip of 11 another embodiment of the nebulizing catheter. In this 12 embodiment, a nebulizing catheter 148 includes a main 13 shaft section 152 and a distal shaft section 156. The 14 distal shaft section 156 is tapered to a tip 160. At the tip 160, a liquid orifice 164 is surrounded by a 16 plurality of gas orifices 168. In a preferred 17 embodiment, there are six gas lumens terminating in the 18 six orifices 168. In this embodiment, the liquid orifice 19 164 has a diameter of approximately .002 inches and the gas orifices 168 each have a diameter of approximately 21 .002 inches. This embodiment is similar to the 22 embodiment of FIG. 11 except that the distal section 156 23 provides for a reduction in the tip size and 24 corresponding modification of the nebulization plume properties. This reduction is preferable as it provides 26 a smaller orifice size.

27 The embodiment of FIG. 15 shows a distal 28 portion of a nebulizing catheter 172. In this 29 embodiment, the nebulizing catheter includes a proximal shaft section 176 and a distal shaft section 180. The 31 proximal shaft section 176 includes a plurality of lumens 32 184. A central one 188 of the plurality of lumens 184 is 33 used to convey liquid medicine and the remainder of the 34 lumens surrounding it are used to convey gas. The distal shaft section 180 connects to the distal end of the 1 proximal shaft section 176 and defines a tapered cavity 2 192 between the distal end of the proximal shaft section 3 176 and a distal orifice 196. At least one of the 4 plurality of lumens 184 is used to convey a pressurized gas that is discharged into the cavity 192. A tubular 6 extension 200 extends the liquid lumen through the cavity 7 192 and distally out the orifice 196. The orifice 196 is 8 sized to provide an annular region around the tubular 9 extension 200 to permit the pressurized gas to flow through to nebulize the liquid medication that exits a 11 distal orifice 204 of the tubular extension 200. In a 12 preferred embodiment, the distal shaft section 180 is 13 composed of stainless steel and the orifice has an I.D.
14 of .025 inches. The tubular extension 200 has an O.D. of .012 inches and an I.D. of .007 inches. This embodiment 16 has the advantage of combining a relatively small distal 17 profile with a relatively large proximal flow channel.
18 Another advantage of this embodiment it that it provides 19 for a balanced airflow around the liquid orifice 204.

FIG. 16 shows yet another embodiment for a tip 21 for a nebulizing catheter. In FIG. 16, a nebulizing 22 catheter 208 has a coaxial configuration similar to the 23 embodiment of FIG. 10 (although it could also have a 24 configuration similar to that of other coaxial embodiments, e.g. FIGS. 11, 14, or 15). In FIG. 16, a 26 thin solid wire or filament 212 is located at a distal 27 end of a liquid orifice 216 located at a distal end of an 28 inner tubular member 220. The tapered wire 212 extends a 29 short distance distally from the distal end of the inner tubular member 220. The tapered wire 212 is located with 31 respect to the liquid orifice 212 so that liquid being 32 conveyed through the inner member 220 continues to flow 33 distally of the distal orifice 216 along the wire 212, 34 i.e. adhering to it by surface tension. Of course, once the liquid reaches a distal tip 224 of the wire 212, it 36 is entrained and nebulized by the gas flow from the 1 annular region 228 defined between the inner tubular 2 member 220 and an outer tubular member 232. As mentioned 3 above, one of the factors that affects the nebulization 4 plume particle size and geometry is the size of the distal liquid orifice. In general, a smaller liquid 6 orifice produces smaller particles and a narrow aerosol 7 plume cone. In the embodiment of FIG. 16, the thin wire 8 212 carries only a small amount of liquid along it so 9 that it functions similarly to an orifice of a very small size. Accordingly, the embodiment of FIG. 16 has the 11 potential for producing an aerosol of very fine 12 particles. In the embodiment of FIG. 16, the outer 13 tubular member has an I.D. of approximately .020 inches.
14 The inner tubular member has an I.D. of approximately .006 inches. The thin wire has an O.D. of approximately 16 .002 inches. The wire or filament 212 may be composed of 17 a metal wire or a polymer wire, such as a polyolefin 18 fiber like Spectra fiber. Alternatively, the filament 19 212 may be composed of a porous or felt-like material, such as nylon or Porex, in which case it may be wider in 21 diameter than if made of a solid material.

22 FIG. 17 shows an alternative embodiment of the 23 embodiment of FIG. 16. In FIG. 17, there is a distal end 24 of a nebulizing catheter 236 having a tapered wire or filament 240 located at the distal end of a lumen of an 26 inner tubular member 244. The tapered wire 240 in this 27 embodiment has a curved shape that is designed to whip in 28 a spiral when it is in a flow of air. In the embodiment 29 of FIG. 17, when pressurized gas flows through the annular region 248, it causes the tapered wire 240 to 31 whip around with a spiral motion. The length of the wire 32 240 is chosen so that it does not impact the wall of the 33 trachea or other airway passage when it moves in a spiral 34 whipping motion. In one embodiment, the wire 240 has a length of approximately 1 - 2 mm. The tapered wire 240 36 carries the liquid out to its tip for entrainment, and 1 the nebulization plume is formed with a conical shape.
2 The width of the plume may be changed by changing the 3 length of the filament 240. The speed of the spiral 4 motion can be controlled by appropriate selection of wire stiffness and air foil shape. In general, the spiral 6 plume produced by the embodiment of FIG. 17 will be wider 7 than the embodiment of FIG. 16 and have less forward 8 velocity. Both these characteristics may be favored in a 9 nebulization catheter.

FIGS. 18 and 19 show another embodiment of the 11 nebulization catheter. In this embodiment, a 12 nebulization catheter 252 has a coaxial configuration 13 formed of an outer tubular member 256 and an inner 14 tubular member 260. A distal plug 264 fits into a distal end of the annular region 268 forming the gas lumen. A
16 plurality of apertures 272 extend through the plug 264 to 17 form distal gas orifices. Located in a lumen 276 defined 18 by the inner tubular member 260 is a retractable wire or 19 pin 280. The wire 280 is preferably a solid wire of a rigid material. For example, the wire may be composed of 21 a metal, such as stainless steel, a polymer, or a 22 radiopaque material. A distal end 284 of the inner 23 member 260 is tapered and may extend distally of the plug 24 264 or alternatively may extend only to the distal end of the inner tubular member 260 or even proximally thereof.
26 The distal end of the inner member 260 terminates in a 27 distal liquid orifice 285. A distal end 286 of the wire 28 280 may also be tapered. The wire 280 is sized with 29 respect to the inner tubular member 260 so that the tapered distal portion 286 of the wire 280 seats against 31 the tapered distal portion 284 of the inner tubular 32 member 260 and thereby seals a distal end of the liquid 33 lumen 276 in a manner similar to a needle valve. The 34 wire 280 is retractable and in a preferred embodiment is operated to reciprocate back and forth to pulse the 36 delivery of liquid out the distal end of the nebulizing 1 catheter 252. The pulsing of aerosol delivery may be 2 adjusted to any suitable time period. In one preferred 3 mode of operation, the aerosol may be delivered only 4 during inhalation by the patient. If the nebulizing catheter 252 is being used with an endotracheal tube and 6 a ventilator, the pulsing of the aerosol delivery may be 7 timed to coincide with the patient's inhalation by an 8 appropriate connection with the ventilator. By limiting 9 the delivery of medicine to only the period of time when the patient is inhaling, the medicine can be delivered 11 more efficiently and with less waste.
12 One preferred way to generate the pulsed 13 aerosol plume with the embodiment of FIGS. 18 and 19 is 14 with a manifold arrangement 287. A proximal end of the wire 280 is fixed to an extendable section 288 of the 16 manifold 287. The wire 280 may be fixed by means of an 17 elastomeric seal 289. Pressurized gas is delivered to a 18 port 290 of the manifold that communicates with the outer 19 tubular member 256 and liquid medicine to be nebulized is delivered to a second port 291 that communicates with the 21 inner tubular member 260. The liquid medicine also fills 22 the volume 292 proximal of the port 291 in the expandable 23 section 288. The wire 280 is connected to the manifold 24 so that the distal end of the wire is biased against the distal end of the inner tubular member by the resilience 26 of the inner tubular member 260 and/or the expandable 27 section 288. Pulsed pressurization of the liquid 28 medicine from the source causes the extendable section 29 288 to reciprocate back and forth as shown by the arrow 293. Since the proximal end of the wire 280 is attached 31 to the expandable section 288 proximal of the port 291, 32 application of pressure pulses to the liquid causes the 33 proximal end of the wire 280 to reciprocate back and 34 forth as well. This causes the distal end of the wire 280 to reciprocate back and forth in the seat 284.
36 Application of pressure pulses to the liquid medicine can 37 be timed to coincide with the patient's inhalation.

1 Alternatively, instead of forming an expandable or 2 compressible section at the manifold, the shaft of the 3 inner tubular member 260 may be formed of a stretchable 4 material so that pressurization of the liquid causes retraction of the wire as the entire shaft elongates.
6 Other alternatives for effecting reciprocating operation 7 of the wire 280 are use of an electro- mechanical, 8 mechanical, hydraulic, or pneumatic actuator to drive the 9 wire. Aside from providing for pulsed delivery of the aerosol, this embodiment of the nebulization catheter has 11 the further advantage that the reciprocating action of 12 the wire may assist in keeping the orifice free of any 13 blockages which may occur, especially with some viscous 14 solutions or suspensions.
In a manner similar to the embodiments 208 and 16 236 of FIGS. 16 and 17, in the embodiment 252 of FIGS. 18 17 and 19, the distal tip of the retractable wire 292 can 18 extend distally from the distal liquid orifice 288 in 19 order to minimize particle size, or alternatively may not extend distally of the distal liquid orifice 292. In one 21 embodiment, the distal tip of the retractable wire may 22 extend distally of the liquid orifice 288 by 23 approximately .2 mm.

24 FIG. 20 shows another embodiment of a nebulizing catheter. In this embodiment, a nebulizing 26 catheter 296 has a main shaft portion 300 with a gas 27 lumen 304 adjacent to a liquid lumen 308. The gas and 28 liquid lumens 304 and 308 flow into a distal cavity 312.
29 The distal cavity 312 is formed by an outer tubular extension 316 that extends distally over and past a 31 distal end 320 of the main shaft portion 300. A filter 32 324 is located in the liquid lumen 308 to filter out any 33 particles in the liquid. The liquid lumen 308 has a step 34 down in diameter immediately distal of the location of the filter,324. An insert plug 328 is located in a 36 distal end of the outer tubular extension 316. The 1 insert plug 328 (which may be a sapphire jewel, for 2 example) has an aperture 332 through it that forms an 3 exit orifice from the cavity 312. The insert plug 328 4 has a conical shaped proximal profile facing the cavity 312. An inner tubular extension 336 fits into the 6 stepped down portion of the liquid lumen 308 and extends 7 the liquid lumen 308 into the cavity 312. A distal end 8 340 of the inner tubular extension 336 terminates in the 9 cavity 312. Since the gas lumen 304 exits into the cavity 312, nebulization of the liquid takes place at the 11 tip of the inner tubular extension 336 inside the cavity 12 312. This region of the cavity 312 is a positive 13 pressure region due to the relative sizes and locations 14 of the apertures. The positive pressure in this region may have the effect of reducing drooling of the liquid 16 medicine as it leaves the orifice of the tubular 17 extension 336. The aerosol exits the catheter 296 via 18 the aperture 332 and the aerosol plume is defined in part 19 by the positive pressure in the cavity 312 and the aperture size. In this embodiment, the main shaft 21 portion and the tubular extension are composed of a 22 suitable plastic such as polyethylene. The filter is 23 composed of multiple 50 m I.D. tubes or similar course 24 filter material. The gas and liquid lumens may each have an I.D. of .010 to .015 inches The inner tubular 26 extension 336 may be formed of polyimide tubing with an 27 I.D. of .004 inches and an O.D. of .010 inches. The 28 outer tubular extension 316 may be formed of a heat 29 shrunk tubing, such as polyethylene. The plug 328 may have an O.D. .087 inches and the aperture 332 in the plug 31 328 may have a diameter of .007 inches.

32 FIG. 21 shows another embodiment of the 33 nebulizing catheter. This embodiment is similar to the 34 embodiment 296 shown in FIG. 20 and accordingly the components are numbered similarly. The embodiment of 36 FIG. 21 differs from the embodiment of FIG. 20 in that 1 the distal end of the inner tubular extension 312 is 2 located in the aperture 332 of the insert plug 328. In 3 the embodiment of FIG. 21, the orifice 332 at the distal 4 end of the tubular extension 336 is in a low pressure, high velocity region as compared to the embodiment of 6 FIG. 20. This has a corresponding effect on plume size 7 and shape as well as possible particle size.

8 FIG. 22 shows yet another embodiment for the 9 nebulizing catheter. In this embodiment, a nebulizing catheter 340 has a main shaft portion 344 that has a gas 11 lumen 348 and a liquid lumen 352. The gas lumen 348 12 terminates distally in a gas orifice 356. Located in the 13 distal end of the liquid lumen 352 is a liquid tubular 14 extension 360. The liquid tubular extension 360 forms an angle so that a distal liquid orifice 364 is in alignment 16 with the flow of gas out the distal gas orifice 356. In 17 this embodiment, the liquid lumen 352 has an I.D. in the 18 range of .010 to .020 inches. The gas lumen 348 has an 19 I.D. of approximately 0.10 to .020 inches. The liquid tubular extension 360 is formed of a stainless steel tube 21 with an O.D. of .018 inches and an I.D. of .012 inches.
22 The distal gas orifice 356 has an I.D. of .010 inches.
23 The stainless steel extension tube 360 forms a right 24 angle so that the distal liquid orifice 364 is at a right angle and aligned with the distal gas orifice 356. The 26 distal gas orifice 356 and the distal liquid orifice 364 27 are positioned as close together as possible, and in one 28 embodiment, these orifices are approximately .010 inches 29 apart.

FIG. 23 shows an alternative embodiment of the 31 nebulization catheter shown in FIG. 22. In this 32 embodiment, the nebulization catheter 340 has an 33 additional lumen 365. This additional lumen 365 may have 34 an I.D. of approximately .020 inches. This additional lumen 365 may be used for an optical fiber viewing scope 1 366 for illumination and visualization of the distal end 2 of the nebulization catheter 340. The optical viewing 3 scope 366 may be permanently installed in the catheter 4 340 or preferably may be removable. A distal end 367 of the lumen 365 is open or covered with a transparent lens 6 so that the area distal of the catheter 340 can be 7 observed via an optical viewing device connected to a 8 proximal end of the optical fiber 366. This enables a 9 physician to observe the alignment of the distal end of the nebulization catheter and also observe the 11 nebulization when it occurs. The gas orifice 356 may be 12 located so that the pressurized gas that is expelled 13 helps to keep the distal end of the viewing lumen 365 14 clear. An optical fiber viewing channel may be incorporated into any of the embodiments of the 16 nebulization catheter disclosed herein. When the 17 additional lumen 365 is occupied by a removable viewing 18 scope, it may be used for other purposes such as pressure 19 sensing, gas sampling, over pressure relief, or other diagnostic or therapeutic purposes. Alternatively, 21 another lumen may be provided for these purposes.
22 The embodiment of FIG. 23 also shows opposing 23 orifices. As in the embodiment of FIG. 22, a tubular 24 extension 360 extends distally of the end of the catheter shaft and is oriented at an angle, e.g. 90 degrees, to 26 the direction of the axis if the catheter shaft. The 27 tubular extension 360 opens to a distal liquid orifice 28 364 from which the liquid being conveyed in the lumen 352 29 exits. In this embodiment, a second tubular extension 363 communicates with the gas lumen 348 and opens to a 31 distal gas orifice 367. The second tubular extension 363 32 is also oriented relative to the axis of the catheter 33 shaft, e.g. by 90 degrees, so that is aimed toward the 34 distal liquid orifice 364 in order to nebulize the liquid exiting from the liquid orifice 367.

1 FIG. 24 shows still another embodiment of the 2 nebulizing catheter. In this embodiment, a nebulizing 3 catheter 368 has a main shaft section 372 with a gas 4 lumen 376 and a liquid lumen 380. Tubular extensions 384 and 388 extend the gas and liquid lumens 376 and 380 from 6 the main shaft section 372 to a distal tip of the 7 catheter 368. The distal portion of the shaft forms a 8 tapered region 392 that surrounds the tubular extensions 9 384 and 388 and causes them to be angled toward each other. The tubular extension 388 for the liquid lumen 11 380 extends slightly distally of the distal end of the 12 tubular extension 384 of the gas lumen 376 so that a 13 distal liquid orifice 396 is in alignment with the flow 14 of gas from a distal gas orifice 400. In this embodiment, the distal liquid orifice 396 has an O.D. of 16 150 microns and an I.D. of 20 microns. The gas orifice 17 400 has an I.D. of approximately .018 inches.

18 FIGS. 25 and 26 show an alternative embodiment 19 of the nebulizing catheter 368 shown in FIG. 24. In FIGS. 25 and 26, the tubular extensions 384 and 388 of 21 the gas lumen 376 and the liquid lumen 380 are formed 22 with sealable tips. Specifically, the gas tubular 23 extension 384 has a sealable tip 408 and the liquid 24 tubular extension 388 has a sealable tip 412.
Alternatively, only the liquid lumen 380 has the sealed 26 tip 412 and the gas lumen 376 has an open distal orifice.
27 The sealable tips may be formed by heating the material 28 from which the tubular extensions are made to reform the 29 walls of the plastic material so as to form a closed slit. This is represented in FIG. 26. When pressurized 31 gas and liquid are conveyed through the lumens 376 and 32 380, the slits forming the tips 408 and 412 dilate 33 thereby permitting the gas and liquid to exit to from the 34 aerosol, as illustrated in FIG. 25. However, when the pressure in the lumens 376 and 380 falls below a 36 threshold, the tips 408 and 412 close thereby sealing off 1 the lumens, as illustrated in FIG. 26. The embodiment 2 404 of the nebulizing catheter is used with pulsation of 3 the gas and/or liquid supplies. In order to pulse the 4 generation of aerosol to coincide with a patient's inhalation, the pressure to the gas and/or the liquid 6 lumens can also be pulsed. When the pressure in either 7 of the lumens falls below a threshold, the tips 408 or 8 412 close. By closing off the flow of liquid at the tip 9 412 during the period when the aerosol is not being generated, it is possible to reduce any drooling from the 11 tip of the catheter.

12 III. Nebulization With Counterflow 13 As mentioned above, control of nebulized 14 particle size and plume shape are important considerations affecting the efficacy of the therapy. In 16 many applications, it is preferable to have as small a 17 particle size as possible combined with as little forward 18 velocity as possible. Some of the embodiments described 19 below accomplish these objectives through use of counterflow arrangements.
21 FIG. 27 shows a nebulization catheter 416 that 22 can be located inside of an endotracheal tube as in the 23 previously described embodiments. The nebulization 24 catheter 416 has a coaxial tubular arrangement with an outer tube 417 surrounding an inner tube 418 so that a 26 liquid delivered from a distal liquid orifice 419 of the 27 inner tube 418 is nebulized by the flow of a pressurized 28 gas delivered in a distal direction from the annular 29 region between the inner and outer tubes at the distal orifice 420 of the outer tube 417. In addition, another 31 lumen 428 extends through the shaft of the nebulization 32 catheter 416. This additional lumen 428 connects to a 33 distal tubular extension 432. The tubular extension 432 34 extends distally of the distal end of the nebulization catheter 416. A distal end 436 of the distal tubular 36 extension 432 curves back on itself so that a distal 1 orifice 440 of the tubular extension 432 is oriented in a 2 proximal direction back at the orifices 419 and 420 of 3 the inner and outer tubes. The additional lumen 428 also 4 carries a pressurized gas which is directed in a proximal direction by the orifice 440 against the direction of the 6 aerosol plume generated by the gas and liquid exiting the 7 orifices 419 and 420. The gas from the additional lumen 8 428 presents a counterflow to the gas from these orifices 9 thereby slowing down the velocity of the particles generated from these orifices. In a preferred 11 embodiment, the distal tubular extension 432 may be 12 formed of a suitable material such as stainless steel 13 needle stock. The O.D. of the nebulization catheter in 14 this embodiment may be similar to the other nebulization catheter embodiments described above, e.g. O.D of 16 approximately .038 inches. The distal tubular extension 17 432 may have an O.D. of approximately .013 inches and an 18 I.D. of approximately .009 inches. In this embodiment, 19 the outer tubular member of the nebulization catheter may have an O.D. of approximately .013 inches and an I.D. of 21 approximately .009 inches and the inner tubular member 22 may have an O.D. of approximately .003 inches and an I.D.
23 of approximately .0015 inches.

24 FIG. 28 shows another embodiment of the present invention for a nebulizing catheter 448 that incorporates 26 a counterflow arrangement. Like the embodiments 27 described above, in this embodiment the nebulizing 28 catheter 448 may be located in an endotracheal tube (not 29 shown). The nebulization catheter 448 has a distal section 452 that curves back on itself. The nebulization 31 catheter 448 has distal orifices 453 and 454 that 32 generate a plume of nebulized particles in a reverse, 33 i.e. proximal, direction. Also located in the 34 nebulization catheter 448 is another lumen 456 for carrying a pressurized gas. The additional lumen 456 has 36 a distal orifice 460 oriented in a distal direction. The 1 distal orifice 460 of the additional lumen 456 is aligned 2 with respect to the distal orifices 452 and 453 of the 3 nebulization catheter 448 so that the flow of gas from 4 the additional lumen 456 slows down the velocity of the nebulization plume generated from the nebulization 6 catheter 448. The aerosol plume generated by the 7 nebulization catheter reverses direction and is delivered 8 to the lungs carried by the inhalation of air through the 9 endotracheal tube or by the flow of gas from the additional lumen 456 or a combination thereof.

11 FIGS. 29 and 30 show another embodiment of a 12 counterflow nebulization catheter arrangement. In FIGS.
13 29 and 30, a nebulizing catheter 464 is used with an 14 endotracheal tube 468. A nebulization catheter 464 has a distal tip 472 from which a liquid medicine delivered 16 from a distal liquid orifice is nebulized by a flow of 17 pressurized gas from a gas orifice located adjacent to 18 the liquid orifice. The nebulizing catheter 464 shown in 19 FIG. 30 extends distally of the endotracheal tube 468 and has a distal section 476 that curves back on itself. The 21 nebulization catheter 464 has distal orifices that 22 generate a plume of nebulized particles in a reverse, 23 i.e. proximal, direction back toward the distal opening 24 of the endotracheal tube 464. In order to maintain a proper reverse orientation and to prevent snagging, the 26 nebulization catheter 464 includes a wire 480 that 27 extends from the tip 472 of the nebulization catheter 28 464. The wire 480 is secured to a portion of the shaft 29 of the nebulization catheter proximal of the tip. The wire 480 can be secured by means of a heat shrunk tube 31 484 located on a shaft 488 of the catheter to hold the 32 end of the wire 480. Although some aerosol may impact 33 the wire 480, a wire having a small diameter is used to 34 minimize losses due to such impaction. Moreover, the overall improved efficiency due to reduction in aerosol 36 impaction on the walls of the trachea or other airway 1 passage is expected to more than compensate for any 2 losses due to impaction on the wire 488.
3 In the embodiment shown in FIG. 30, the 4 nebulization catheter 464 directs a nebulization plume in a reverse direction back toward the distal opening of the 6 endotracheal tube 468. The nebulization plume from the 7 nebulization catheter encounters the flow of air from the 8 endotracheal tube 468 during the inhalation phase of the 9 patient. The inhalation of air through the endotracheal tube 468 causes the nebulized medicine to reverse 11 direction and carries it to the lungs. It is noted that 12 the reversal of direction of the nebulization plume has 13 the effect of minimizing the aerosol particle velocity.
14 It is also noted in the embodiment shown in FIG. 30 that the endotracheal tube 468 is provided with an inflatable 16 cuff 492 located around the distal portion.

17 IV. Other Nebulization Catheter Embodiments 18 In the embodiments described above, the 19 velocity of the nebulization plume was reduced by use of a counterflow of gas in an opposite direction. In the 21 embodiment of FIGS. 31 and 32, the velocity of the 22 nebulization particles is reduced in another manner. In 23 FIG. 31 a nebulization catheter 496 has a liquid lumen 24 500 terminating in a distal liquid orifice 504 and a one or more gas lumens 508 terminating in one or more distal 26 gas orifices 512. The liquid delivered through the 27 liquid lumen 500 is nebulized by the pressurized gas 28 flowing out the plurality of gas orifices 512. The 29 nebulization catheter 496 also includes one or more additional lumens 516 that terminate in additional distal 31 orifices 520. These lumens 516 are used to deliver a 32 vacuum (negative pressure) at the distal orifices 520.
33 The vacuum is provided by a suitable vacuum source (not 34 shown) connected to proximal ends of the additional lumens 516. The vacuum delivered by the additional 36 lumens 516 helps withdraw the pressurized gas delivered 1 by the lumen 508 after it has nebulized the liquid 2 delivered by the liquid lumen 500. Without the vacuum 3 provided by the additional lumens 516, the pressurized 4 gas delivered by the distal gas orifices 512 may continue to impart energy to the nebulized liquid particles 6 delivered by the distal liquid orifice 504 thereby 7 causing them to be propelled with a forward velocity.
8 Instead, the vacuum scavenges at least some of the 9 pressurized gas after it has nebulized the liquid so that the forward velocity of the liquid particles can be 11 reduced. In order to facilitate scavenging of the 12 pressurized gas, the distal liquid orifice 504, the 13 distal gas orifices 512, and the distal vacuum orifices 14 520 all open into a distal cavity 524 formed by an outer tubular extension 528 of the nebulizing catheter 496.
16 The distal extension 528 has a closed distal end 532 with 17 a small aperture 536 located therein to emit the 18 nebulized liquid particles with a low forward velocity.
19 With the nebulizing gas removed, the aerosol particles are carried forward primarily only by their inertia.

21 The embodiment of the nebulization catheter 496 22 shown in FIG. 31 includes a vacuum line 516 as a means to 23 reduce the forward velocity of the nebulization plume.
24 Provision of vacuum line 516 to the tip of a nebulization catheter 496 can serve an additional function of 26 balancing the gas flow and pressure delivered to the 27 airway in which the nebulization catheter is located.
28 This may be useful to prevent excess airway pressure 29 generated by the catheter flow particularly in smaller airways or where a neutral flow balance may be desired.
31 This may particularly be desired when the nebulization 32 catheter is provided with an inflatable cuff that 33 occludes the airway passage at the distal end of the 34= nebulization catheter. The flow balance may be controlled with a closed or partially closed pumping 36 system where a gas pump 537 with a single intake and 1 outlet would be connected to the respective vacuum and 2 gas supply lumens 516 and 508 of the catheter. Both the 3 driving gas and vacuum would be balanced and regulated by 4 the pump speed. A vacuum or pressure vent port 538 could be incorporated into the respective vacuum or pressure 6 lines if a positive or negative flow balance was desired.
7 If flow balance is a concern, but not velocity reduction, 8 it is not important where the air flow is removed at the 9 distal tip of the catheter and accordingly, the distal end extension 532 may not be needed. Alternatively, a 11 flow balance may be maintained with separate a pressure 12 and vacuum source through the use of regulators, 13 restrictive capillary tubes or orifices, or flow sensors 14 and flow control valves incorporated into the pressure and vacuum supply lines.

16 FIG. 33 shows another embodiment of a 17 nebulization catheter 540 that incorporates a feature to 18 reduce the forward velocity of the nebulized liquid 19 particles. The nebulization catheter 540 has a main shaft portion 544 having a liquid lumen 548 and a 21 pressurized gas lumen 552. The lumens 548 and 552 22 terminate in distal orifices 556 and 560. The 23 pressurized gas flow from the orifice 560 nebulizes the 24 liquid exiting from the orifice 556. The nebulization catheter 540 includes a distal spacer tube 564. The 26 spacer tube 564 has a length of approximately 2-3 mm and 27 an inside diameter larger than the outside diameter of 28 the nebulization catheter shaft 544. Because the inside 29 diameter of the spacer tube 564 is larger than the airflow lumen and orifice, the velocity of air and 31 entrained particles is reduced as they pass through the 32 spacer tube 564 and out a distal opening 568 thereof.
33 In addition, the spacer tube 564 may have one or more 34 apertures or holes 572 through a wall thereof close to the proximal end of the spacer tube at its connection to 36 the main shaft 544. These holes 572 draw in air to the 1 inside of the spacer tube 564 thereby causing drag due to 2 turbulence and reducing the velocity of the aerosol as it 3 exits the spacer tube. The holes 572 may also slow the 4 flow of particles through the spacer tube by causing drag turbulence.
6 The spacer tube 564 also serves to protect the 7 distal orifices 556 and 560 of the nebulization catheter 8 from coming into contact with any part of the 9 endotracheal tube, trachea, or other airway passage thereby helping to maintain optimum tip operation and to 11 prevent damage to it during handling and insertion. In 12 an alternative embodiment, if only the tip protection 13 feature is desired, the spacer tube 564 of FIG. 33 may be 14 provided without the apertures 572. In such an alternative embodiment, the spacer tube 564 may be 16 provided in a shorter length, e.g. 1 mm.

17 FIG. 34 shows another embodiment of a 18 nebulization catheter 576 used with an endotracheal tube 19 580. The endotracheal tube 580 may be a conventional endotracheal tube. The nebulization catheter 576 21 provides for a nebulization plume with,a reduced forward 22 velocity by imparting a spiral component to the liquid 23 particle flow. The nebulization catheter 576 has a 24 distal tip 584 from which a liquid medicine delivered from a distal liquid orifice is nebulized by a flow of 26 pressurized gas from a gas orifice located adjacent to 27 the liquid orifice. The nebulization catheter 576 is 28 positioned coaxially in the endotracheal tube 580. A
29 centering device 585 may be used to aid in centering the nebulization catheter 576. Located along a portion of 31 the nebulization catheter 576 proximal from the tip 584 32 is a second gas orifice 588. This second gas orifice 588 33 may open to the same gas lumen that communicates with the 34 nebulizing gas orifice at the distal tip 584 or alternatively, the second gas orifice 588 may connect to 36 another, separate gas lumen. The second gas orifice 588 1 is oriented to direct a pressurized flow of gas in a 2 spiral, distal direction along the distal end of the 3 nebulization catheter 576. To accomplish this, the 4 second gas orifice 588 may be formed by an inclined opening or with a deflection foil to direct the flow of 6 gas in the appropriate spiral direction. The spiral flow 7 of pressurized gas travels along the distal portion of 8 the nebulizing catheter 576 inside the endotracheal tube 9 580. The spiral flow of gas entrains the aerosol generated from the distal end 584 of the nebulizing 11 catheter imparting a spiral flow component to the aerosol 12 plume. This has the effect of reducing the forward 13 velocity component of the liquid particle flow as it 14 leaves the endotracheal tube 580.

FIG. 35 shows an alternative method for using 16 the nebulization catheter 576 of FIG. 34. In FIG. 35, 17 the nebulization catheter 576 is shown extended distally 18 of the distal end of the endotracheal tube 580 so that 19 the distal portion of the nebulization catheter 576 including the second gas orifice 588 is located in an 21 airway passage. Taking into account the size of the 22 airway passage, the nebulization catheter 576 with the 23 second gas orifice 588 would operate similarly to the 24 method shown in FIG. 34 and generate a spiral gas flow to reduce the forward velocity of the aerosol plume.

26 Another embodiment of a nebulizing catheter 592 27 is shown in FIGS. 36 and 37. This embodiment of the 28 nebulizing catheter 592 can be used with a separate 29 endotracheal tube (not shown). The nebulizing catheter 592 includes a main shaft 596 having a central lumen 600 31 and one or more additional lumens 604 located around the 32 central lumen 600. In this embodiment, the central lumen 33 600 is used for the flow of a pressurized gas and the 34 additional peripheral lumens 604 are used for the delivery of the liquid medicine. The lumens 600 and 604 1 terminate distally in orifices 608 and 612, respectively.
2 Located at a distal end of the nebulizing catheter 592 3 and immediately adjacent the orifices 608 and 612 is a 4 diffuser 616. In one embodiment, the diffuser 616 is composed of a generally disk-shaped body that is sized to 6 deflect the flow of gas from the orifice 608 of the 7 central lumen 600 past the liquid orifices 612 thereby 8 nebulizing the liquid medicine. A small gap (or venturi 9 area) 620 between the diffuser 616 and the distal end of the main shaft section 596 of the catheter 92 provides 11 favorable flow characteristics for generating the 12 aerosol. The diffuser 616 may be connected to a 13 retaining wire 624 that is located in the central lumen 14 600. The retaining wire 624 may be used to secure the diffuser 616 to the distal end of the nebulizing catheter 16 592. Also, the retaining wire 624 may be used to pulse 17 the generation of aerosol by reciprocation of the 18 diffuser. It is noted that the aerosol produced by this 19 embodiment has a substantially radial velocity component and may have only a small forward velocity component. In 21 addition, a centering device, such as wings 625, may be 22 attached to the diffuser 616.

23 FIG. 38 shows an alternative embodiment of the 24 diffuser 616. In FIG. 38, the diffuser 616 is formed of a loop that has its ends located in two apertures in the 26 nebulization catheter shaft tip and a middle portion 27 directly in front of the distal gas orifice 608. The 28 loop may be formed of a metal or polymer wire or other 29 material. The loop could be formed by an extrusion method or molded.

31 Referring to FIG. 39, there is an alternative 32 embodiment of the nebulization catheter system. A
33 nebulization catheter 627 is located in an endotracheal 34 tube 628. The nebulization catheter 627 includes a coaxially arranged outer tube 629, a middle tube 630, and 1 an inner tube 631. Liquid delivered through a lumen of 2 the inner tube 631 is nebulized by pressurized gas 3 delivered in the annular region 632 between the inner 4 tube 631 and the middle tube 630. In addition, pressurized gas is also delivered from a secondary gas 6 supply that communicates with the annular region 633 7 between the middle tube 630 and the outer tube 629. The 8 secondary gas supply may be used to help provide the 9 desired plume shape and velocity. For example, the secondary gas supply delivered from the outer tube 629 11 can be used to provide a coaxial sheath of air that helps 12 minimize impaction of the nebulized aerosol on the walls 13 of the trachea or other airway passage. Alternatively, 14 the secondary air supply may be used to impart additional forward velocity to the aerosol plume. With the 16 embodiment of FIG. 39, the additional air flow can be 17 provided by the secondary gas supply via region 633.
18 In the embodiments discussed above, 19 nebulization is provided at a distal tip of a catheter by directing a pressurized gas from a distal orifice across 21 another distal orifice from which the liquid medicine is 22 delivered. As shown in several of the embodiments above, 23 one way to deliver the liquid from the distal orifice is 24 via a lumen that extends through the catheter to a proximal end. This construction provides efficient 26 operation for many types of medication delivery. In many 27 cases, the distal liquid medicine orifice is subject to a 28 negative pressure due to the pressurized gas flow across 29 it. This negative pressure may in many applications be sufficient to draw the liquid out of the orifice in order 31 to nebulize it. If pulsing of the aerosol is desired, 32 the pressure of the gas lumen can be pulsed thereby 33 resulting in pulsed generation of the aerosol. By 34 increasing the gas pressure, it may be possible to also increase the aerosol output.

1 In other situations, it may be preferable to 2 apply a positive pressure to the liquid, such as at the 3 proximal end of the liquid lumen, in order to deliver 4 liquid from the distal liquid orifice, it is necessary.
This positive pressure applied to the liquid lumen may be 6 the same as that applied to the gas lumen (e.g. 35-50 7 psi) or alternatively may be different (less than the gas 8 lumen). If it is desired to pulse the nebulization of 9 the liquid, this can be accomplished by applying pulses of pressure to the column of liquid via the proximal end 11 of the liquid lumen or reservoir. It may also be 12 preferred to synchronize the pressurization of the gas in 13 the gas lumen with the pressurization of the liquid 14 lumen. In addition to applying the positive pressure to the liquid lumen in pulses to generate a pulsed aerosol 16 from the distal orifice, if it may be preferred in an 17 alternative embodiment to apply a small negative pressure 18 immediately after each positive pressure pulse in order 19 to draw the liquid at the distal orifice back into the liquid lumen to thereby avoid drooling. In a preferred 21 embodiment, the portion of the nebulization catheter in 22 which the liquid lumen is formed may be composed of a 23 relatively low compliance material to transmit pressure 24 pulses to the distal end with minimum attenuation.
A full length liquid lumen may have 26 disadvantages in certain situations. For example, 27 pulsing of the liquid from the distal orifice may not 28 correspond to or follow closely with the application of 29 pressure to the proximal end due to attenuation of the pressure pulse over the length of the catheter. In 31 addition, applying pressure to the proximal end of the 32 liquid lumen in order to transmit pressure to discharge 33 the liquid from a distal orifice requires that the lumen 34 be filled with the liquid. In some situations, this is more medicine than would be required by the patient and 36 might result in waste.

1 The embodiment in FIG. 40 addresses these 2 concerns by controlling the pressurization of the liquid 3 as close as possible to the distal liquid orifice, 4 thereby reducing the effects of catheter compliance and attenuation. In FIG. 40, a nebulization catheter 652 has 6 a main body 656 having a gas lumen 660 that extends from 7 a proximal end (not shown) to a distal gas orifice 664.
8 The main body 656 also includes a distal liquid medicine 9 reservoir 668. In the embodiment shown in FIG. 40, the liquid reservoir 668 is located in a distal portion of 11 the main shaft 656 of the catheter 652. The liquid 12 reservoir 668 is preferably close to the distal tip of 13 the nebulizing catheter 652. The liquid reservoir 668 is 14 filled with the medicine to be delivered. If the amount of medicine is small in volume, the liquid reservoir may 16 also be correspondingly'small. This embodiment is 17 especially suitable for the delivery of small volumes of 18 medicine such as .1 to .5 ml, e.g. single use. The 19 reservoir 668 may be pre-filled during the manufacturing stage of the catheter. The reservoir 668 may be formed 21 by plugging a lumen of the catheter at a distal location.
22 Alternatively, the liquid reservoir 668 may also extend 23 back to the proximal end of the catheter, thereby forming 24 a liquid lumen, and communicate with a proximal port as described with respect to the other embodiments discussed 26 herein. This may be required if the lumen is made of a 27 non-compliant material. In yet another alternative 28 embodiment, the liquid reservoir may be formed in a 29 balloon located externally of the catheter shaft 656.
A filter 672 and plug 676 occupy positions in 31 the distal end of the liquid lumen/reservoir 668. A
32 distal tubular extension 680 extends from the plug 676 33 and communicates with the liquid lumen/reservoir 668.
34 The tubular extension 680 has a distal orifice 684 aligned with the distal gas orifice 664 so that a 36 pressurized gas exiting the gas orifice 664 nebulizes the 37 liquid exiting the liquid orifice 684. The distal liquid 1 orifice may have a sealable cap or wax-like covering 2 associated therewith that can be opened when the 3 nebulization catheter is put into use. In a distal 4 section of the main shaft 656 of the catheter 652, the gas lumen 660 and the liquid lumen 668 are separated by a 6 flexible, distendable wall or membrane 688. In the 7 embodiment of FIG. 40, pulsing of the aerosol is 8 accomplished by pulsing of the gas pressure in the gas 9 lumen 660. When the pressure in the gas lumen 660 is high, it causes the flexible wall 688 between the gas and 11 liquids lumens 660 and 668 to distend into the liquid 12 lumen 668. This is represented by the dashed line in 13 FIG. 40. When this occurs, the pressure from the gas 14 lumen 660 is transmitted to the liquid lumen 668 and liquid medicine is forced out the distal liquid orifice 16 684. When the pressure applied to the gas lumen 660 is 17 low, the distendable wall 688 recovers its original 18 position. It is noted that when the distendable wall 680 19 recovers its original position, it may cause a negative pressure at the distal liquid orifice 684 which may cause 21 the liquid to withdraw slightly into the tubular 22 extension 680 thereby reducing the occurrence of liquid 23 drooling at the tip. In addition, it is noted that the 24 delivery of liquid from the distal liquid orifice 680 may not occur immediately upon application of a high gas 26 pressure to the gas orifice since it will take some time 27 for the bladder 688 to distend. This means that gas will 28 be flowing steadily at a high pressure from the distal 29 gas orifice'when the liquid begins to flow from the distal liquid orifice. This also may provide cleaner 31 aerosol delivery and reduce the occurrence of drooling of 32 liquid at the tip.
33 An alternative embodiment of the nebulization 34 catheter 652 shown in FIG. 40 may be made using a flexible, but inelastic material for the bladder wall 36 688. If the bladder wall 688 were flexible, but 37 inelastic, the pressurized gas passing past the liquid 1 orifice 684 would create a negative pressure (venturi 2 effect) thereby drawing out the liquid and nebulizing it.
3 A continuous or preferably an intermittent gas supply to 4 the venturi area would provide this negative pressure.
The bladder wall may be provided with a vent to 6 facilitate discharge.
7 In order to manufacture a nebulization catheter 8 with compliant and non-compliant regions, as described 9 above, the catheter may be co-extruded using different compounds or polymers to optimize the physical properties 11 of the different wall sections. It may be preferred to 12 use high energy radiation to crosslink the polymer 13 material in the formation of the bladder wall.
14 V. Alignment of the Aerosol Plume The embodiments described above are directed to 16 developing an optimum nebulization plume. It is further 17 recognized that another factor that contributes to the 18 efficiency of the nebulization is the position of the 19 nebulization catheter relative to the anatomical environment. For example, even if the nebulization 21 catheter being used develops an optimal plume, the 22 delivery efficiency of the catheter may be significantly 23 impaired if the plume is directed into the wall of the 24 endotracheal tube, the trachea or other airway passage.
Accordingly, proper location, orientation, and alignment 26 of the nebulization catheter in the anatomy can be an 27 important factor contributing the delivery of medicine 28 via a nebulization catheter. In general, it is 29 preferable to align the catheter coaxially in the airway passage in which it is located.
31 It is also noted that an endotracheal tube, if 32 present, can adversely effect delivery of aerosol from a 33 separate nebulization catheter. For example, an 34 endotracheal tube has an inner diameter that is smaller than the diameter of the trachea so that if the 36 nebulization takes place inside the endotracheal tube, a 1 portion of the aerosol may impact the inner wall of the 2 endotracheal tube and thereby be wasted. Most 3 conventional endotracheal tubes have a curved distal end 4 that is relatively rigid so that when it is in place in the trachea of a patient, the distal end of the 6 endotracheal tube is oriented off center. This can 7 affect the orientation of a nebulization catheter located 8 in the endotracheal tube causing it direct its aerosol 9 into the trachea wall even if the nebulization catheter is positioned so that its distal end is located distally 11 of the endotracheal tube. In general, it is desirable to 12 allow the aerosol particles to avoid impaction for 13 several centimeters after the aerosol is produced so that 14 the aerosol particles can lose their velocity and become entrained in the inspiratory airflow.
16 The embodiment of the invention in FIG. 41 is 17 directed at providing improved alignment of a 18 nebulization catheter in a patient's trachea. In FIG.
19 41, an endotracheal tube 700 is positioned in a trachea 704 of a patient. The endotracheal tube 700 is of a type 21 that has an inflatable cuff 708 located around a distal 22 exterior side to facilitate positioning and alignment of 23 the endotracheal tube 700 in the trachea 696. Extending 24 through and out of a distal end of the endotracheal tube 700 is a nebulization catheter 712. The nebulization 26 catheter 712 may be similar to any of the embodiments of 27 the nebulization catheter described above. Located 28 around a distal portion 716 of the nebulization catheter 29 712 is a spring centering apparatus 720. The spring centering apparatus 720 includes a retainer ring 724 31 fixed to the shaft of the nebulization catheter 712 and a 32 plurality of arms 728 connected to the ring 724. In one 33 embodiment, there are three arms 726. The arms 726 are 34 flexible and resilient. The arms 726 may be made of a spring tempered metal or a suitable plastic. Located at 36 the end of each of the arms 726 opposite its connection 37 to the ring 724 is a ball 727. The spring centering 1 apparatus 720 is deployed by first positioning the 2 nebulizing catheter 712 including the spring centering 3 apparatus in the lumen 728 of the endotracheal tube 700.
4 The arms 726 are formed so that they assume a size larger than the diameter of the trachea or airway passage.
6 Accordingly, when the centering device is positioned in 7 the endotracheal tube 700, the arms are resiliently 8 deformed into a compressed configuration with the balls 9 727 close to the shaft of the nebulizing catheter 712.
To deploy the centering device, the nebulizing catheter 11 712 is advanced out the distal end of the endotracheal 12 tube 700. When the balls 727 are advanced out the 13 endotracheal tube 700, they spring out to an expanded 14 size and engage the walls of the trachea or other airway passage. The balls 727 provide a relatively smooth 16 surface to limit irritation or injury to the trachea 17 walls or other airway passage. With the arms expanded, 18 the nebulizing catheter is centered in the trachea or 19 other airway passage so that a plume discharged from a distal end of the nebulizing catheter has minimal contact 21 with the walls of the trachea or other airway passage.
22 When it is necessary to remove the nebulizing catheter 23 712, it can be withdrawn in a proximal direction back 24 into the endotracheal tube 700. In a preferred embodiment, the arms are formed of a thin resilient wire 26 or polymer, preferably less than approximately .015 27 inches in diameter. The arms and/or the balls may be 28 made of, or coated with, a radiopaque material. It is an 29 advantage of the embodiment of the centering device shown in FIG. 41 that it is located somewhat in advance of the 31 distal end of the nebulization catheter. This positions 32 the arms 726 of the centering device in the portion of 33 the trachea or other airway passage into which the 34 aerosol will be initially flowing. Thus, the centering device orients the distal tip of the nebulization 36 catheter relative to the portion of the trachea or other 1 airway passage beyond the distal tip thereby helping to 2 reduce impaction along this portion.
3 FIG. 42 shows an alternative embodiment of the 4 nebulization catheter. A nebulization catheter 729 is used with an endotracheal tube as described above. The 6 nebulization catheter 729 includes a centering device 7 730. The centering device 730 includes a plurality of 8 arms 731 that are formed to resiliently extend outward 9 from the axis of the catheter shaft to engage the wall of the patient's trachea or airway passage or the interior 11 of an endotracheal tube depending upon the desired 12 location of the distal end of the nebulization catheter.
13 At the ends of each of the arms 731 are balls 732. The 14 proximal ends of the arms 731 are formed of wires 733 that extend through lumens 734 in the shaft of the 16 catheter 729. Each of the lumens 734 has a distal 17 opening 735 from which an arm can extend. The distal 18 openings are approximately .10 - 1 cm from the distal end 19 of the catheter shaft. The proximal ends of the wires 733 exit the lumens 734 of the nebulization catheter via 21 openings 736 that are close to the proximal end of the 22 catheter in a portion of the catheter that would normally 23 be outside the patient's body during use. Thus, the 24 proximal ends of the wires 733 are accessible to the physician during use. By pulling and pushing on the 26 proximal ends of the wires 733, the portion of the arms 27 731 that extend from the openings 735 can be adjusted.
28 Thus, the arms 731 can be adjusted from a fully retracted 29 to a fully advanced position by pulling or pushing on the proximal ends of the wires 733. In addition, since the 31 proximal ends can of the wires 733 be adjusted in any 32 intermediate position between the fully retracted and 33 fully advanced positions, the physician can adjust the 34 size of the centering device 730 to any appropriate size, as desired. Because the wires 733 should assuine a 36 desired shape when advanced out of the lumens in which 37 they are contained during positioning, it is preferable 1 that they be formed of a material that has shape memory 2 properties so that the desired expanded shape can be 3 imparted to the wires during manufacture. In one 4 embodiment, the wires may be formed of nitinol.
In one preferred embodiment, a second centering 6 device 737 is also provided. The second centering device 7 737 is located on the shaft of the nebulization catheter 8 729 proximally from the first centering device 730. The 9 second centering device 737 may be formed of resilient wings formed of a material such as plastic or metal that 11 extend radially outward from the shaft. The second (or 12 proximal) centering device 737 helps keep the distal 13 portion of the catheter 729 in alignment.

14 FIG. 43 shows another alternative embodiment of the present invention. A nebulizing catheter 738 is 16 shown which may be similar to the catheter 20 of FIG. 1.
17 The nebulizing catheter 738 includes a centering device 18 739. The centering device 739 includes a wire loop 740 19 located at a distal end of the catheter. One end 741 of the loop 740 connects to the distal end of the nebulizing 21 catheter shaft. The other end 742 of the wire loop 740 22 enters an opening 743 in the shaft that communicates with 23 a lumen 744 that extends to a proximal end of the 24 catheter 738. A proximal end 745 of the wire exits the lumen 744 via an opening 746 in a proximal portion of the 26 nebulizing catheter which is normally outside the 27 patient's body during use. The size of the wire loop 740 28 can be adjusted by advancing or withdrawing the proximal 29 end 745 of the wire. In this embodiment, it can be determined that the centering device is fully retracted 31 when the wire 745 cannot be withdrawn any further. The 32 position of the distal end of the nebulization catheter 33 can also be determined by the resistance to further 34 retraction caused when the loops or arms engage the distal end of the endotracheal tube. When in an expanded 36 size, the wire loop 740 engages the walls of the trachea 1 or airway passage or the interior of the endotracheal 2 tube depending upon where the distal end of the 3 nebulizing catheter is positioned. The size of the wire 4 loop 740 can be adjusted from a fully reduced size to a fully expanded size as well as intermediate sizes. With 6 the embodiment of FIG. 43, the size of the loop can be 7 adjusted to different size airway passages in different 8 patients or alternatively the size of the loops can be 9 adjusted to different airway passages in the same patient if the physician desires relocating the nebulizing 11 catheter to different locations in a patient's 12 respiratory tract. In a one preferred embodiment, more 13 than one wire loop may be provided at the distal end of 14 the nebulizing catheter. It is noted that the wire loop 740 of this embodiment may also be used in for 16 facilitating positioning over a guide wire in a manner 17 similar to loop 106 shown in FIG. 9.

18 FIGS. 44 and 45 show another alternative 19 embodiment of the present invention. A nebulizing catheter 747 has a shaft portion 748 and a wire loop 749 21 extending from a distal end of the shaft 748. In this 22 embodiment, the wire loop 749 is connected at each end 23 750 and 751 to the distal end of the catheter shaft 748.
24 A retractable sheath 752 is positioned over the nebulizing catheter shaft 748. The sheath 752 can be 26 advanced and withdrawn relative to the catheter shaft 27 748. When it is desired to maneuver the nebulizing 28 catheter into a desired position in the respiratory tract 29 of a patient, the sheath 752 is advanced over the loop 749 to maintain a low profile, as shown in FIG. 45. When 31 the distal end of the nebulizing catheter is suitably 32 positioned, the sheath 752 is then retracted, as shown in 33 FIG. 44, allowing the loop 749 to expand to its expanded 34 size to center and align the distal end of the nebulizing catheter in the respiratory tract. In one embodiment, 1 the loop 749 is formed of a superelastic material such as 2 nitinol.
3 As noted above, proper positioning and 4 alignment of the nebulization catheter can be an important factor affecting drug delivery efficiency. In 6 general, it is preferable to position the tip of the 7 nebulizing catheter as closely to the central region of 8 the trachea (or other respiratory passage, such as the 9 bronchi) as possible. It is further noted that even if the catheter can be centered relative to the trachea, if 11 a section proximal to a centering device is misaligned, 12 it can affect the directional orientation of the tip.
13 This situation is represented in FIG. 46 in which a 14 nebulizing catheter 753 is centered, but the tip is not properly aimed to provide an optimum plume. This 16 potential problem can be overcome by using an embodiment 17 of the invention shown in FIG. 47. In FIG. 47, a 18 nebulizing catheter 754 is located in a trachea 755 of a 19 patient. The nebulizing catheter 754 extends out the end of an endotracheal tube 756. A first centering apparatus 21 757 is located on a main shaft 760 of the nebulizing 22 catheter 754 close to the distal end 764. The first 23 centering device 757 may be similar to the centering 24 devices shown in FIGS. 41 - 45. A second centering device 768 is located axially along the nebulizing 26 catheter shaft 760 proximally from the first centering 27 device 757. The second centering device 768 may be the 28 same as the first centering device 757. As shown in FIG.
29 47, the two centering devices 757 and 768 not only serve to position the nebulization catheter 7754 centrally in 31 the trachea, but also serve to align the nebulizing 32 catheter tip to expel the plume along a central axis of 33 the trachea.
34 The proximal centering device 768 may be substituted by another type of centering device or may 36 employ the endotracheal tube 756 for this purpose, as 37 shown in FIG. 48. If the endotracheal tube is used to 1 assist in centering the nebulization catheter, it may 2 incorporate a distal, elongated occlusion cuff 772 or 3 balloon to coaxially align it accurately in the trachea.
4 Most conventional endotracheal tubes are provided with a curvature to facilitate positioning the trachea of a 6 patient. In addition, most conventional endotracheal 7 tubes are relatively stiff. These factors may result in 8 the misalignment of the distal end of the endotracheal 9 tube relative to a patient's trachea as illustrated in FIGS. 46 and 47. In order to use the endotracheal tube 11 for centering of the nebulization catheter, it is 12 preferable to make the tip of the endotracheal tube 13 straighter andJor more flexible than in conventional 14 endotracheal tubes to ensure proper concentricity with the occlusion balloon and the trachea. An endotracheal 16 tube with a straighter and more flexible tip is shown in 17 FIG. 48. In addition, the endotracheal tube may be 18 provided with a centering or aiming device 776 for 19 aligning the nebulization catheter 754. In the embodiment of FIG. 48, the aiming device 776 is formed by 21 a plurality of flexible or resilient wings the extend 22 from the wall of the endotracheal tube 756 toward an 23 axially central position.
24 Appropriate centering and aiming of the nebulization catheter can be affected by anatomical 26 factors. It is noted that in some circumstances, it is 27 preferable to position the distal tip of the nebulization 28 catheter into either bronchus of the lungs or even into 29 separate bronchia. Positioning of the nebulizing tip closer to the alveoli may enhance drug delivery 31 efficiency. In a situation in which it is desired to 32 place the nebulizer tip in both bronchi of the lungs, a 33 nebulizing catheter 780 with dual tips can be employed, 34 as shown in FIG. 49. When using a dual tip catheter such as shown in FIG. 49, centering and aiming can be 36 important considerations because of the narrower air 37 passages in each of the bronchi. To provide for 1 centering and aiming of a dual tip nebulizing catheter, 2 each of the tips 784 and 788 may be provided with its own 3 centering apparatus, such as 792 and 796. These 4 centering devices may be similar to the centering devices described above. Alternatively, the centering devices 6 792 and 796 may be formed of arms or struts, made of a 7 flexible or resilient material, that bow out from the 8 shafts of each of the tips 784 and 788, as shown. These 9 struts may be formed with a shorter length in order to fit into smaller airway passages or alternatively they 11 may be made to provide a range of deployment sizes to 12 accommodate different airway passages.
13 As an alternative to providing a nebulizing 14 catheter with dual tips 784 and 788 as shown in FIG. 49, if delivery of aerosolized medicine into separate 16 branches of the lungs is desired, it may be preferred to 17 use a nebulizing catheter with a single nozzle tip that 18 has multiple orifices or jets aimed toward the desired 19 branches.
With respect to all the centering devices 21 described above, it is noted that some aerosol may impact 22 the wires or loops that form the centering devices and 23 accordingly, the centering devices are preferably 24 constructed of wires or other materials having a small diameter or cross section to minimize losses due to such 26 impaction. Moreover, the overall improved efficiency due 27 to the reduction in aerosol impaction on the walls of the 28 trachea or'other airway passage is expected to more than 29 compensate for amy losses due to impaction on the centering device.
31 Another alternative means for centering the 32 distal end of a nebulization catheter in the air passage 33 is to use part of the pressurized gas for a pneumatic 34 centering device. Air jets generated from two or more outward directed orifices spaced evenly around the outer 36 circumference of the nebulizing catheter near the tip can 37 be used to center the catheter in the airway. This 1 alternative may help avoid irritation and provide 2 additional advantages compared to physical centering 3 devices.
4 Another alternative way to help center the nebulizing catheter in the patient's airway passage is to 6 use a balloon or wire centering device placed near the 7 nebulizing catheter tip. The balloon or wire centering 8 device can be temporarily inflated to double check the 9 placement.of the nebulizing catheter tip in relation to the endotracheal tube tip. To use this feature the 11 nebulizing catheter is advanced beyond the endotracheal 12 tube tip using markings on the proximal shaft to judge 13 the distance. The centering device or balloon would then 14 be expanded to a diameter larger than the endotracheal tube and the catheter retracted until the centering 16 device or balloon could be felt engaging with the 17 endotracheal tube tip or until the endotracheal airflow 18 was obstructed.

19 VI. Operation and Flow Control As mentioned above, the driving gas used to 21 pressurize the gas lumen may be pure (e.g. 100%) oxygen 22 at a pressure of 35-50 psi. Other gases and pressures 23 may be used with suitable adjustments to provide for the 24 desired particle size. The pressurized gas also may be humidified by a bubbler or other suitable means and 26 warmed, if necessary.
27 Regarding the liquid lumen, one way to deliver 28 the liquid drug through the nebulizing catheter is by a 29 manually operated syringe. To delivery a liquid drug in this manner, a syringe containing the liquid medicine to 31 be nebulized is connected to the liquid port on the 32 manifold connected to a proximal end of the nebulizing 33 catheter. Then, the liquid is injected while the 34 pressuring gas is being supplied to the nebulizing catheter via the gas inlet port on the nebulizing 36 catheter manifold. Using a manually operated syringe is 1 reliable, easy to use, and may be preferred when it is 2 desired to deliver only a small amount of medication.
3 In a preferred embodiment, the liquid drug is 4 delivered to the nebulizing catheter from a pressurized source. A.pressurized source for the liquid medicine can 6 provide for a generally higher and more uniform pressure.
7 A high pressure assists in clearing any blockages that 8 may occlude the liquid lumen. Pressurization of the 9 liquid lumen also can ensure that all the liquid drug is evacuated from the catheter tip. In addition, use of a 11 liquid pressurization source can provide for drug 12 delivery for a longer period of time or a drug delivery 13 that is timed or pulsed to coincide with operation of a 14 ventilator, if used. In a preferred embodiment, the same pressure source (at 50 psi) that is used to provide the 16 gas pressurization can also be used to provide for 17 pressurization of the liquid. Some ventilators have an 18 auxiliary port that are used for externally located 19 nebulizers. The pressure flow from this auxiliary port may be used as a pressure source to drive the liquid and 21 gas supplies of the embodiments of the nebulizing 22 catheter considered herein. Alternatively, a sensor 23 located in the flow from this auxiliary port may be used 24 to trigger another control device that operates the pressurized liquid and gas supplies.
26 In a preferred embodiment, the generation of 27 the aerosol can be synchronized with the inhalation of 28 the patient. In one embodiment, this can be accomplished 29 with a manually operable control gas valve on the gas pressure line to the liquid input port. This may be 31 suitable when the medicine can be delivered in a short 32 period of time, e.g. a few respiratory cycles.
33 Alternatively, when it is preferred to deliver the 34 medicine for an extended period of time, it may be preferred to employ a system that can automatically 36 deliver medicine via the nebulizer from a source of 37 liquid medicine. In such a system, the gas and/or liquid 1 flow are triggered by the patient's respiratory cycle 2 with the use of an electronic pressure sensor and relay 3 actuator.
4 An important factor relating to effective delivery of medication via a nebulizing catheter is the 6 flow control system for pressurizing and supplying the 7 gas and liquid to the proximal end of the nebulization 8 catheter. In many circumstances, it is envisioned that 9 medication will be delivered to the patient via a nebulization catheter that is in place in the patient 11 over an extended period of time, such as several hours or 12 days. In such circumstances, it would be preferred to 13 use a system that automatically delivers the proper 14 dosage of medication from a supply of the medicine to the patient at the proper rate, and further that can operate 16 automatically and unattended. Further, it would be 17 preferred to provide a means to detect when the supply is 18 running low so that either the nebulization catheter can 19 be disconnected or a new supply provided. FIGS. 50 and 51 show several embodiments of a reservoir and 21 pressurization system for use with a nebulizing catheter.
22 Referring to FIG. 50, a reservoir and 23 pressurization assembly 800 is connected to a proximal 24 end of a nebulization catheter. The nebulization catheter may be similar to any of the embodiments 26 described above. The assembly 800 has a gas inlet port 27 804 that can connect to an external pressurized gas 28 supply. The external pressurized gas supply may be the 29 main gas supply of the hospital or may be provided by another unit. The external gas supply may provide oxygen 31 at 50 psi. The gas inlet port 804 communicates with an 32 airflow passageway 808 defined by and extending through 33 the assembly 800. The assembly 800 includes a gas output 34 port 812 that communicates with the fluid flow passageway 808 and which connects to a gas inlet port of the 36 nebulization catheter (not shown). The gas output port 37 812 is located immediately downstream of the gas inlet 1 port 804. Located in the fluid flow passageway 808 2 downstream of the gas outlet port 812 is a filter 816.
3 The filter 816 is preferably a hydrophobic filter that 4 allows the passage of gas but which would prevent the backflow of any liquid. Located downstream of the filter 6 816 in the fluid flow passageway 808 is an injection port 7 and reservoir 820. This port 820 communicates with a 8 supply of the liquid fluid medication to be supplied to 9 the nebulizing catheter. Located next in the fluid flow passageway 808 is a capillary tube drug reservoir 824.
11 The capillary tube reservoir 824 is comprised of a length 12 of plastic tubing adapted to hold a supply of the liquid 13 medication to be delivered. In the embodiment shown, the 14 capillary tube reservoir consists of a helical coil of transparent tubing. Located downstream of the capillary 16 tubing reservoir 824 is a liquid outlet 828 that connects 17 to a liquid inlet port of the nebulization catheter (not 18 shown). With the embodiment shown in FIG. 50, the 19 transparent capillary tubing 824 provides a convenient and reliable way to ascertain the supply of medication to 21 the nebulizing catheter. The capillary tubing because of 22 its length is capable of containing a suitable supply of 23 the medication. When the attending medical personnel 24 observe that the medication is about to run out, a new supply can be readily provided. The clear capillary tube 26 allows easy visualization of the drug flow by watching 27 the gas-drug meniscus travel down the tube. Instead of 28 relying on direct observation by medical personnel, the 29 capillary tubing may be used with an automatic detection device, e.g. a photocell, that provides an alarm to the 31 medical personnel upon detection that the medication is 32 running out in the capillary tubing or that the meniscus 33 has ceased moving due to a blockage. A blockage may also 34 be detected by detection of an increase in pressure.

FIGS. 51 and 52 show another embodiment of a 36 fluid reservoir and pressurization assembly 832. This 1 embodiment includes a gas inlet 836, a fluid flow 2 passageway 840, a liquid medicine supply vent 844, a 3 filter 848, a capillary channel section 852, and an 4 outlet port 856. In this embodiment, the filter 848 is located downstream of the filling vent 844. The filter 6 848 allows the pressurized gas to push the liquid drug 7 during use but prevents the liquid drug from backing up 8 to the vent during filling. In this embodiment, a second 9 injection port 860 is provided downstream of the capillary section 852 and a second filter 864 is located 11 downstream of the second injection port 860. The second 12 filter 864 is preferably a filter having approximately a 13 20 m retention. Also, in this embodiment, the capillary 14 section 852 may be composed of a planar section 865. The planar section 865 may be a piece of plastic having a 16 winding channel molded, routed or otherwise formed 17 therein. The planar section 868 is preferably colored to 18 provide suitable contrast with the liquid solution 19 flowing therethrough. A transparent flat plastic cover is positioned over the winding channel of the planar 21 section 865 to form the closed channel of the capillary 22 section. The fluid channel in the capillary section 23 preferably has an I.D. of approximately 2 mm. The second 24 inlet port 864 provides an additional means to add medication to the nebulizing catheter liquid flow. When 26 the capillary channel in the section 852 has been filled, 27 the gas is used to pressurize the tube and force the 28 fluid to the catheter tip. The second filter 864 acts as 29 a restrictive orifice to precisely meter the flow to the nebulizing catheter. The clear capillary channel allows 31 easy visualization of the drug flow by watching the gas-32 drug meniscus travel down the tube. The narrow tube 33 makes the flow appear to move quickly even at slow 34 delivery rates. Thus, any flow interruption can be easily observed. The capillary tubing sectiori also 36 ensures that almost 100% of the drug is delivered to the 1 catheter tip since there is no dead space in the line 2 except at the injection port 860.
3 During ventilation of a patient with an 4 endotracheal tube, especially when intubation that takes place for a long period of time, it is considered 6 desirable to humidify the air being delivered. When a 7 nebulization catheter is used for delivery of medicine, 8 either in conjunction with an endotracheal tube or even 9 without an endotracheal tube, it is possible to utilize the nebulization catheter for providing humidification in 11 addition to medicine delivery. An embodiment of a flow 12 delivery system for a nebulizing catheter incorporating 13 humidification is shown in FIG. 53. A suitably large 14 reservoir 866 holds sterile water or saline. The reservoir 866 is connected to the liquid supply lumen 867 16 of a nebulization catheter 868. Solution is drawn into 17 the nebulization catheter 868 from the reservoir 866 by 18 negative pressure at the catheter tip, gravity, a pump in 19 the solution supply line distal of the reservoir, or by pressurizing the reservoir by a suitable means.
21 Medicine may be added to the humidification 22 water in at the following ways. In a first alternative, 23 the medicine is added to the isotonic saline in the 24 solution reservoir 866 thereby providing for high dilution and slow, continuous delivery of the medicine 26 along with the water. In second alternative, the 27 medicine is introduced into the solution supply line 867 28 via an injection port 869 between the reservoir 866 and 29 the liquid lumen of the catheter 868. The medicine may be delivered to the injection port of the solution supply 31 line from a solution reservoir system such as system 800 32 of FIG. 50. Using this latter alternative, a more 33 concentrated dose of the medicine can be delivered at the 34 specific time preferred by the physician. It may also be preferable to include a molecular sieve, check valve or 36 air trap 870 between the reservoir 866 and the injection 1 port to the to ensure that the medicine cannot flow or 2 diffuse backwards into the reservoir 866.
3 When delivering medicine to the lungs or when 4 delivering water for humidification, it may be desired to heat the liquid prior to delivery. This may especially 6 be appropriate since expanding gases which are associated 7 with the nebulization of liquids may remove heat from the 8 body. In order to address this concern, a heating 9 element 871 may be associated with the liquid supply line 867 to the nebulizing catheter 868. This heating element 11 871 may include an electric coil wound around the supply 12 line 867 or may use a heated water flow in a tubing wound 13 around the supply line 867. The heating element 871 may 14 be used in embodiments that provide for humidification as well as those that do not. Alternatively, the heating 16 element 871 may be associated with the gas supply line or 17 with the liquid reservoir 866, 18 It is generally considered preferable to 19 operate the nebulizing catheter so as to generate an aerosol that is carried by a patient's inhalation to the 21 lungs. This requires a pulsing of the aerosol generation 22 so that it is timed to coincide with the inhalation of 23 the patient. If the patient is intubated, the timing of 24 the nebulization can be7synchronized with the operation of the ventilator. It is recognized that it may be 26 preferable to begin the nebulization slightly in advance 27 of, at, or slightly after, the beginning of the 28 inhalation period in order to account for the distance 29 between the nebulization tip and the alveoli. Also, it may be preferable to stop the nebulization slightly 31 before the end of the inhalation period in order to avoid 32 wasting aerosol after the inhalation flow has stopped.
33 This continuous pulsing of the aerosol can be 34 accomplished by a system 872 as shown in FIGS. 54 and 55.
FIGS. 54 and 55 show a portion of the flow control system 36 for a nebulizing catheter. A flow line 876 has an inlet 37 880 and an outlet 884. The flow line 876 may be formed 1 of a soft (e.g. compliant) tube. The inlet 880 connects 2 to the source of liquid medicine and in particular may 3 attach to the liquid outlet (828 or 856) of the liquid 4 reservoirs shown in FIGS. 50 - 52. The flow line outlet 884 in FIGS. 54 and 55 connects to the liquid inlet port 6 on the manifold of the nebulizing catheter, such as port 7 32 in FIGS. 1 and 2. Located around a portion of the 8 flow line 876 is an actuator piston 888. The actuator 9 piston 888 includes a solenoid pinch valve 892 that can impinge upon the portion of the liquid flow line 876 11 extending therethrough thereby pinching it off. The 12 actuator piston 888 is connected-to and operated by a 13 controller that receives input from the ventilator (such 14 as from the auxiliary port used for an external nebulizer) so that the actuator piston 888 is operated to 16 open and close the flow line synchronous with the 17 inhalation and exhalation phases of the ventilator.
18 Instead of a solenoid piston, a metering valve or 19 reversible syringe pump may be used.
In a preferred embodiment, the flow control 21 system 872 uses a dual solenoid arrangement to provide a 22 draw-back feature. Pulsing of the liquid flow by 23 actuation of the actuator piston 888 may result in some 24 liquid being left at the distal nebulizer liquid orifice when the pressure is turned off. This may result in 26 small amounts of liquid drooling from the distal liquid 27 orifice tip since the liquid is not being expelled under 28 controlled pressure conditions. In order to limit the 29 occurrence of such drooling, a draw back feature is provided in the flow control system. The draw back 31 feature is provided by a second solenoid 896 which is 32 associated with a bladder 900 that communicates with the 33 flow line 876. The bladder 900 communicates with the 34 flow control line 876 downstream of the actuator piston 888. A small amount of fluid (liquid/air) occupies the 36 bladder 900. The bladder is composed of an elastic 37 material that is formed with a tendency to recover to an 1 expanded size. When the actuator piston 888 opens to 2 allow the flow of fluid to the distal end of the 3 nebulizing catheter, the second solenoid 896 moves to a 4 closed position thereby compressing the bladder 900 and squeezing fluid out of it into the fluid flow line 876, 6 as shown in FIG. 54. During the exhalation stage of the 7 ventilation cycle, the actuator piston 888 closes to shut 8 off the flow of fluid to the distal end of the nebulizing 9 catheter. When the actuator piston 888 closes, the second solenoid 896 opens, as shown in FIG. 55. This 11 allows the bladder 900 to resiliently recover to its 12 expanded size, and when it does, it draws fluid into it 13 from the fluid flow line 876. Because the fluid flow 14 line 876 is closed proximally at the actuator piston 888, when the bladder draws fluid into it from the fluid flow 16 line 876, it draws fluid from the distal end of the fluid 17 flow line that connects to the nebulizing catheter liquid 18 lumen. This causes the entire column of liquid in the 19 liquid lumen of the nebulizing catheter to move slightly in a reverse direction (i.e. proximally) thereby moving 21 the liquid away from the distal orifice. In this manner, 22 the flow control system of FIGS. 54 and 55 allows the 23 draw back of liquid in the flow line in a reverse 24 direction during the exhalation phase of the ventilator when the liquid flow line is shut off.

26 VII. Selective Nebulization Therapy Delivery 27 When delivering medication with a nebulizing 28 catheter, it may be desirable to deliver the medication 29 to only one of the bronchi of the lungs and not the other or to only certain bronchia and not others. A reason for 31 this type of selective therapy may be that only one area 32 of the lungs requires medication. An embodiment of the 33 invention shown in FIG. 56 facilitates selective delivery 34 of a medication via a nebulizing catheter to only one bronchus. In FIG. 56, an endotracheal tube 904 is 36 positioned in a trachea 908 of a patient. A nebulizing 1 catheter 912 is positioned in the endotracheal tube 904.
2 This nebulizing catheter 904 may be similar to the 3 embodiments described above. This nebulizing catheter 4 904 may even be of the type that is non-removably incorporated into the endotracheal tube. A second 6 catheter 916 extends distally of the endotracheal tube 7 904. The second catheter 916 may be positioned in the 8 ventilation lumen 920 of the endotracheal tube 904. The 9 second catheter 916 includes a lumen through which a low flow pressurized gas can be conveyed. A proximal end of 11 the second catheter 916 extends out of the proximal end 12 of the endotracheal tube 904 through a suitable fitting, 13 such as the fitting described in U.S. Pat. No. 5,078,131 14 (Foley). A suitable source of pressurized gas is attached to a proximal end of the second catheter 916.
16 This gas source may be the same gas source used for the 17 pressurized gas lumen of the nebulization catheter 912.
18 A distal end 928 of the second catheter 916 is positioned 19 in the bronchus 932 other than the bronchus to which it is desired to deliver nebulized medication. Pressurized 21 gas is delivered through the second catheter 916 out an 22 orifice 936 in the distal end thereof. The delivery of 23 pressurized gas out the distal end 936 of the second 24 catheter 916 causes the pressure level in the bronchus 932 to be slightly greater than in the other bronchus.
26 Accordingly, when the nebulizing catheter 912 generates 27 an aerosol of liquid medicine, it will tend to flow with 28 the inhalation stream from the endotracheal tube 904 to 29 the bronchus other than the one with the second catheter 916. In this manner, one of the bronchi of the lungs, or 31 even selected bronchia, can be selectively medicated 32 using a single nebulization catheter positioned in the 33 endotracheal tube.

34 VIII. Timing of Nebulization As mentioned before, in order to deliver the 36 nebulized medicine to the lungs, it is preferred that the 1 medicine is carried by the inhalation of the patient. A
2 number of factors affect the efficiency of the medicine 3 delivered this way. The following embodiments are 4 directed to improving drug delivery efficiency taking into account some of these factors.
6 If the patient is intubated, it may be possible 7 to synchronize the timing of the nebulization pulse with 8 the patient's ventilation. In one embodiment, this may 9 be accomplished by providing an interface between the ventilator and the nebulizer. In some circumstances it 11 may be preferred to provide other means for triggering 12 the nebulization. For example, the ventilator being used 13 may not provide a suitable interface. Also, the 14 ventilator may not provide sufficiently accurate information concerning the patient's respiration to 16 enable the nebulization catheter to operate with highest 17 efficiency. In such situations, it may be preferred to 18 utilize one or more separate sensors to obtain 19 information that can be used to trigger and operate the nebulization catheter.
21 Referring to FIG. 57, there is a nebulizing 22 catheter 944 positioned in an endotracheal tube 948 23 located in the trachea 952 of a patient. A proximal end 24 of the endotracheal tube 948 is connected to a ventilator 956. In order to obtain physiological information 26 concerning the patient's respiration for use in timing 27 the generation of nebulization pulses by the nebulization 28 catheter 944, one or more sensors may be used. For 29 example, a first sensor 960 may be located on a distal end of the endotracheal tube 948. In addition, a sensor 31 964 may be positioned on the nebulization catheter 944.
32 Another sensor 968 may be positioned on a separate 33 device, such as a separate catheter 972 which is located 34 further distally in the respiratory system. In addition, a sensor 976 may be positioned in the ventilator circuit 36 of the ventilator 956 or in a ventilator auxiliary port, 37 if available, or elsewhere on the patient. These sensors 1 960, 964, 968, and 976 may be types of sensors that 2 measure pressure, flow or a physiological parameter of 3 the patient, such as muscle contraction, 4 electophysiological activity, etc. In alternative embodiments, one or more of these sensors may be used.
6 FIGS. 58 and 59 show alternative embodiments of 7 nebulization catheters that incorporate sensors. In FIG.
8 58, a nebulization catheter 980 is shown. This 9 nebulization catheter 980 may be similar to the nebulization catheter in FIG. 11. In FIG. 58, a main 11 shaft 984 includes a plurality of lumens with a centrally 12 located lumen 988 used to deliver a liquid medicine and a 13 plurality of lumens 992 located peripherally around it 14 used to deliver a pressurized gas. One of the peripheral lumens 996 is not used for pressurized gas delivery, but 16 instead is used for sensing purposes. This may be 17 accomplished by forming an aperture 1000 through a wall 18 of the main shaft 984. The aperture communicates with 19 the sensing lumen 996. The aperture 1000 may be open or may be covered with a flexible diaphragm that permits 21 transmission of pressure across it. A pressure sensing 22 device may be located at a proximal end of the nebulizing 23 catheter. The pressure at the distal end of the 24 nebulizing catheter can be sensed by the proximally located sensing device via the sensing lumen 996. This 26 could rely on pneumatic sensing of the distal air 27 pressure. Because of the effect of the distal gas 28 pressurization orifice, pressure sensing through the 29 sensing lumen 996 may be used for purposes of gross overpressure for safety purposes. Alternatively, the 31 pressure sensing lumen 996 may be used during periods of 32 time when a pressurizing gas is not being delivered to 33 sense the patient's physiological airway pressure.
34 FIG. 59 shows another embodiment of a pressure sensing nebulization catheter. This embodiment is 36 similar to the embodiment of FIG. 58 except that a sensor 37 1004 is located at a distal end of the catheter 980, 1 specifically in the aperture 1000. In this embodiment, 2 the sensor 1004 is a pressure transducer. Wire leads 3 1008 extend proximally from the sensor 1004 via the lumen 4 996. Instead of measuring pressure, the sensor 1004 could measure the flow at the distal end of the catheter.
6 This may be accomplished by piezoelectric, optical, Hall 7 effect, or other types of sensor technologies. The 8 sensor may also be of a fiber optic type.
9 Although the embodiments of FIGS. 58 and 59 show sensing apparatuses associated with a nebulization 11 catheter, these same types of sensors could also be used 12 in the endotracheal tube 948, the separate catheter 972, 13 or the ventilator 956 of FIG. 57 or the ventilator 14 circuit.
The sensor outputs information to a controller 16 1012 that operates the flow control portion 1013 of the 17 nebulization catheter system. The flow control portion 18 may include the flow control assembly 872 (shown in FIG.
19 55) as well as include the control functions for gas pressurization. The controller 1012 may have preset 21 triggering parameters or may be user adjustable. The 22 controller 1012 may use airway flow, pressure, or 23 physiological activity as a basis for controlling the 24 flow control assembly 1013. The controller 1012 may provide for pulsing based upon any one of the following 26 modes: (1) a controlled volume (bolus) of medicine is 27 delivered with each pulse; (2) medicine is delivered 28 until a physiological condition is sensed, e.g.
29 exhalation; or (3) medicine is delivered for a fixable time interval, e.g. 2 seconds. These modes of operation 31 may be selectable by the physician based upon the 32 preferred treatment taking into account the patient's 33 condition, the type of medicine being delivered, etc.
34 It may also be desired to regulate the delivery of aerosol so that it is not delivered with every 36 inhalation. As mentioned above, one concern with 37 delivery of an expanding gas is the cooling effect that 659,02-72 it may have on the body. This can be a factor with high gas flow rates. Accordingly, it may be preferable to deliver aerosol on every other inhalation or every third inhalation, and so on. Alternatively, it may be preferred to deliver aerosol for certain periods of time, e.g. 5 minutes every hour. Therefore, by alternating aerosol delivery, the cooling effect associated with it can be reduced.

IX. Alternative Embodiments A. Nebulizing Catheter Incorporated in Endotracheal Tube The various embodiments of nebulizing catheters, disclosed above, have been described as being either adapted for use in conjunction with a separate endotracheal tube, or adapted to be used without an endotracheal tube. If used with an endotracheal tube, the embodiments of the nebulizing catheter disclosed above are preferably removable from the endotracheal tube if one is present. It is noted that many of the embodiments of the present invention disclosed herein may also be used in conjunction with a nebulization catheter that is non-removable from an endotracheal tube, i.e. in which the nebulizing catheter is incorporated into and forms part of the endotracheal tube. An endotracheal tube that provides for nebulized medication delivery is described in U.S. Patent No. 5,438,982 of Dr. Neil R. MacIntyre.
According to a system developed by Dr. MacIntyre, there is provided an endotracheal tube that provides for nebulization of a medication at a distal end thereof. According to Dr. MacIntyre's system, an endotracheal tube includes two additional, separate lumens, in addition to its main ventilation lumen used for the patient's breathing airflow.
A medication in a 1 liquid form is conveyed through one of the additional 2 lumens and a pressurized gas is conveyed through the 3 other lumen. The two additional lumens have distal 4 openings near the distal end of the endotracheal tube airflow lumen. The distal opening of the pressurized gas 6 lumen directs the pressurized gas across the distal 7 medication lumen opening thereby nebulizing the liquid 8 medication so that it can be delivered to the patient's 9 lungs. It is intended that the present invention covers embodiments of nebulization catheters that are non-11 removable relative to an endotracheal tube.

12 B. Aerosol Generation with Porous Material 13 FIG. 60 shows another catheter 1060 for 14 producing an aerosol. The catheter 1060 generates an aerosol, or aerosol-like plume by use of a porous 16 material or sponge located in a lumen of the catheter.
17 The catheter 1060 has a main shaft 1064 with a lumen 1068 18 through which liquid medicine is conveyed under pressure 19 and a lumen 1072 through which a gas is conveyed under pressure. A porous material 1076 is located in a distal 21 end of the shaft 1064 so that both lumens 1068 and 1072 22 convey their contents into the porous material 1076. The 23 porous material 1076 may be a porous polyethylene made by 24 Porex. Alternatively, the porous material may be a polymer sponge or other polymer material. Located in the 26 main shaft 1064 distal of the porous 1076 is an end cap 27 1080 with an orifice 1084 located therein. The orifice 28 is small and maintains a positive back pressure in the 29 catheter shaft and porous material area. The end cap 1080 is separated from the distal side of the porous 31 material 1076 by a small gap 1082. The liquid and gas 32 delivered under pressure to the porous material 1076 33 migrate through the porous across the gap 1082 toward the 34 aperture 1084. The liquid and gas become intermixed under pressure and as they are expelled from the fine tip 36 orifice the gas expands and disperses the liquid 1 particles into fine droplets. Upon discharging through 2 the aperture 1084, the medicine forms tiny droplets, e.g.
3 an aerosol. The aerosol is conveyed to the lungs of the 4 patient in a manner similar to that described in the embodiments above. An advantage of using a porous 6 material or sponge at the distal liquid orifice is that 7 it reduces drooling of the liquid.

8 C. Secondary Aerosol Generation 9 In some situations it may be desirable to modify the primary aerosol spray generated by a 11 nebulization catheter. One way that this can be 12 accomplished is by causing the primary aerosol spray to 13 impact upon a baffle placed in its path, the velocity and 14 direction of the spray can be altered and the size of the distribution of the aerosol can be modified creating a 16 secondary aerosol. Impaction upon a properly located 17 baffle can break up large aerosol particles creating a 18 finer aerosol mist. The baffle also deflects or diffuses 19 the airstream carrying the particles reducing their forward velocity and altering their direction. This can 21 lessen impaction on the carina or airways and enhance the 22 entrainment of the particles into the inspiratory flow.
23 Embodiments of nebulizing catheters incorporating an 24 impaction baffle to provide a secondary aerosol are shown in FIGS. 61-64.
26 Referring to FIG. 61, a nebulization catheter 27 1140 has a gas lumen 1142 and a liquid lumen 1144 located 28 in a shaft 1146 of the catheter. The gas lumen 1142 29 conveys a pressurized gas to a distal gas orifice 1148 and the liquid lumen 1144 conveys liquid to a distal 31 liquid orifice 1150. A baffle 1152 connects to a baffle 32 extension tube 1154 so that the baffle 1152 is located 33 distally of the liquid orifice 1150. The baffle 1152 is 34 preferably located as close to the solution orifice 1150 as possible without interfering with the generation of 36 the primary aerosol.

1 Some of the primary aerosol that is not broken 2 into fine particles may remain on the baffle 1152 and 3 build up over time forming a thin liquid film on the 4 surface of the baffle 1152. If this film is left to build up, it will form droplets that either fall or are 6 blown off the baffle. These droplets may become quite 7 large and of little or no therapeutic value representing 8 a waste of the solution.
9 In order to recirculate this film of solution, the baffle 1152 may be used to collect and return the 11 liquid solution to a liquid supply lumen 1144 To achieve 12 this, the baffle may have with one or more orifices 1158 13 or porous material on its surface of the baffle 1152 for 14 the collection of the film of solution. The orifices 1158 drain into or through the baffle, and are in fluid 16 communication with the solution supply lumen 1144 via a 17 lumen located inside of the extension tube 1154. The 18 lumen inside the extension tube 1154 may communicate 19 directly with the solution lumen 1144 or extension thereof.
21 In the embodiment of FIG. 61, the negative 22 pressure generated at the nebulization orifice 1150 by 23 the gas flow over it is used to draw the recirculated 24 solution from the baffle recirculation orifice 1158 via the lumen in the extension 1154 and out the liquid 26 orifice 1150 again. In this case, the recirculation 27 orifices 1158 or surface should be in an area of higher 28 ambient pressure than the solution orifice 1150 to cause 29 the recirculation of the fluid. This may be accomplished by locating the collection orifices 1158 on a distal side 31 of the baffle 1152 opposite the solution and gas orifices 32 1150 and 1148. The flow of new solution (from the 33 proximally located solution reservoir) pumped into the 34 solution lumen 1144 should be less than the flow drawn from the solution orifice 1150 to ensure that least some 36 of the solution from the baffle 1152 is recirculated to 37 the orifice 1150.

1 FIG. 62 shows another embodiment of a 2 nebulization catheter that incorporates a baffle for the 3 purpose of generating a secondary aerosol. This 4 embodiment is similar to the nebulization catheter in FIG. 61 with the exception that the recirculated fluid is 6 drawn back into a recirculation lumen 1160 in the 7 catheter shaft 1146. The recirculation lumen 1160 8 communicates with the liquid lumen 1144 at a junction 9 1162 at which location the recirculated solution is mixed with newly supplied liquid in the solution lumen 1144.
11 FIG. 63 shows another alternative embodiment.
12 This embodiment is similar to the embodiment of FIG. 62 13 except that the recirculated solution is routed from the 14 baffle 1152 to the recirculation lumen 1160 and then to a separate solution orifice for re-nebulization. This 16 dedicated solution orifice 1161 is also located at the 17 catheter tip near a gas orifice 1148 to produce 18 nebulization. The aerosol generated from this separate 19 orifice 1161 is directed into the common baffle 1158 to break it into smaller particles and a portion of the 21 solution will again remain on the baffle and be 22 recirculated. This approach can eliminate the 23 difficulties of balancing the flow of new and 24 recirculated solution to a single solution orifice.
Referring to FIG. 64, there is another 26 embodiment of a nebulizing catheter incorporating a 27 baffle for the generation of a secondary aerosol. In 28 this embodiment, a nebulizing catheter 1170 has a shaft 29 1172 with a liquid lumen 1174 connected to a liquid supply 1176. A gas lumen 1178 connects to a pressured 31 gas source 1180. The liquid lumen 1174 communicates with 32 a distal liquid orifice 1182 and the gas lumen 33 communicates with a distal gas orifice 1184. A baffle 34 1186 is located in front of the liquid orifice 1182.
Aerosol impacting on the baffle 1186 produces a secondary 36 aerosol that flows around the baffle 1186. A residue 37 film of liquid migrates around the baffle 1186 and enters 1 into baffle orifices 1190 located on the distal side of 2 the baffle 1186. The baffle orifices 1190 communicate 3 with a recirculation lumen 1192 that extends through the 4 catheter shaft to a reservoir 1194 located outside of the body where the recirculated solution is combined with 6 non-recirculated solution pumped from a proximal drug 7 reservoir. The flow of recirculated and non-recirculated 8 solution into the system should be carefully balanced to 9 match the amount of aerosol generated. To achieve this, flow metering and pumping strategies can be employed.
11 D. Nebulization Catheter with 12 Pressurized Propellant-Drug Canister 13 In the embodiments described above, medicine is 14 delivered in liquid form to the distal liquid orifice.
In another embodiment, illustrated in the diagram of FIG.
16 65, the medicine may be mixed with a propellant and 17 maintained under pressure and delivered under pressure to 18 the distal tip of a nebulizing catheter 1198. A
19 pressured medicine-liquid propellant mixture could be supplied from a pressurized canister 1200 such as those 21 used as a component of a metered or non-metered dose 22 inhaler. By using a propellant, an aerosol could be 23 generated from the distal end 1202 of the catheter even 24 without the addition of the pressurized nebulizing gas.
However, the delivery of pressurized gas 1204 from the 26 distal end of the nebulization catheter would be used to 27 assist in breaking up any larger medicine particles and 28 also assist dispersing the aerosolized drug solution 29 delivered through the catheter as well as help shape the aerosol plume. For example, the delivery of the 31 pressurized, nebulizing gas may assist in shielding the 32 aerosol generated by the medicine-liquid propellant 33 mixture and help avoid losses due to impaction.
34 E. Nebulizing Function Incorporated in Suction Catheter 1 As mentioned above, the nebulizing catheter can 2 be incorporated into another device, such as an 3 endotracheal tube, either removably or non-removably.
4 Another such device into which a nebulizing catheter can be adapted is a suction or aspiration catheter. A
6 suction catheter is sometimes used in conjunction with 7 patients who are intubated. A suction catheter has an 8 O.D. and a length such that it can be inserted through 9 the ventilation lumen of an endotracheal tube. The suction catheter is used to aspirate fluids and mucin 11 secretions that collect in the respiratory tract of in 12 the endotracheal tube of a patient who is intubated. A
13 conventional suction catheter is inserted down the 14 ventilation lumen of the endotracheal tube and out the distal end. A mucolytic agent may be instilled as a 16 liquid via a lumen of the suction catheter to help in the 17 withdrawal of mucin from the trachea or bronchi. The 18 suction catheter may then be withdrawn from the 19 endotracheal tube and either disposed or retained in a sterile sheath connected to a proximal end of the 21 endotracheal tube so that it can be reinserted into the 22 endotracheal tube again.
23 A nebulizing catheter can be incorporated into 24 a suction catheter so that a single device can perform both the functions of aspiration and nebulization for 26 aerosol delivery. In an alternative embodiment of the 27 present invention, the nebulizing catheter, such as 28 described above, could be incorporated into a suction 29 catheter so that a single catheter can provide both functions. This could be accomplished by provided any of 31 the embodiments of the nebulization catheter described 32 above with a separate lumen for the purpose of providing 33 a suction to withdraw fluid from a patient's respiratory 34 tract. Combining the functions of a suction catheter and nebulization catheter into a single device has the 36 advantages of avoiding the expense of separate products 1 as well as avoiding the inconvenience of inserting and 2 withdrawing separate devices.
3 Embodiments of a suction catheter combined with 4 a nebulization catheter are shown catheter is FIGS. 66-73. FIGS. 66-70 show a suction catheter assembly 1220.
6 The suction catheter assembly 1220 includes a suction 7 catheter shaft 1222 slidably located inside of a flexible 8 sheath 1224. A suction lumen 1225 extends through the 9 suction catheter shaft 1222. A proximal manifold 1226 includes a port 1228 for connecting a vacuum source to 11 the suction catheter lumen 1225. A valve 1230 operates 12 to open and close the port 1228. A distal sleeve 1232 13 provides for connecting to an endotracheal tube such that 14 the suction catheter shaft 1222 can be inserted into the endotracheal tube by pushing the proximal manifold 1226 16 toward the distal sleeve 1232. The distal sleeve 1232 17 may include a manifold for connection to a flush port 18 1233. A seal 1235 located in the sleeve 1232 closely 19 bears on the suction catheter shaft to remove mucous or other unwanted materials that can be removed via the 21 flush port 1233. The shaft of the suction catheter may 22 be provided with a low friction, e.g. hydrophilic, 23 coating to reduce adhesion of mucous.
24 The suction catheter assembly 1220 includes two additional lumens 1234 and 1236. These lumens 1234 and 26 1236 are located in a wall of the suction catheter shaft 27 1222. These lumens 1234 and 1236 communicate with distal 28 orifices 1238 and 1240 located at a distal end of the 29 suction catheter shaft 1222. These lumens 1234 and 1236 are used to deliver a liquid medicine and a pressurized 31 gas for nebulizing the liquid medicine, as described 32 above. Also located at a distal end of the suction 33 catheter shaft 1222 are suction openings 1242.
34 The suction catheter assembly 1220 can be used in a conventional manner to remove mucin from the trachea 36 and from the bronchi. The suction catheter assembly 1220 37 can also be used to deliver medicines to the lungs as an 1 aerosol by means of the nebulizing lumens 1234 and 1236.
2 The nebulizing lumens can also be used to deliver 3 mucolytic agents as an aerosol. Because the fine aerosol 4 delivered by the nebulizing lumens can be carried by a patient's inspiratory airflow into the bronchi, the 6 mucolytic agent can be delivered further into bronchi 7 compared to a suction catheter that merely instills or 8 generates a coarse spray of a mucolytic agent. In 9 addition, the flow velocity produced by the gas pressurization lumen may be used to assist in breaking up 11 mucous at the end of the suction catheter.
12 When using the suction catheter assembly 1220, 13 it can be positioned so that a distal end of the suction 14 catheter shaft 1222 is close to the distal end of the endotracheal tube 1250 as shown in FIG. 68 or 16 alternatively the suction catheter shaft 1222 can be 17 positioned so that it extends past the distal end of the 18 endotracheal tube 1250 as shown in FIG. 70. As shown in 19 FIG. 70, the suction catheter shaft 1220 may be formed with a distal curvature so that the distal end can be 21 brought into proximity with the tracheal wall.
22 Rather than incorporate the nebulizing lumens 23 into the wall of the suction catheter, it may be 24 preferably in many situations to use a conventional suction catheter with a stand-alone nebulizing catheter.
26 The stand-alone nebulizing catheter may be similar to any 27 of the embodiments described above. A suction catheter 28 and a nebulizing catheter can readily be used together 29 with the alternative versions of the manifolds shown in FIGS. 71-73.
31 Referring to FIG. 71, an endotracheal tube 1252 32 has a proximal end with a single port 1254. A suction 33 catheter 1256 has a distal manifold 1258. The distal 34 manifold 1256 could be formed as part of the suction catheter 1256 or could be provided as a separate 36 component. The suction catheter manifold 1258 connects 37 to the single port 1254 of the endotracheal tube 1252.

1 The manifold 1258 has a first port 1260 for connecting to 2 a ventilator and a second port 1264 for connecting to a 3 proximal end of a nebulizing catheter 1266. As shown in 4 FIG. 71, the nebulizing catheter 1266 includes a sterile sheath 1268 which is similar to the sheath included on 6 the suction catheter 1262. In the embodiment of FIG. 71, 7 the suction catheter 1256 and the nebulizing catheter 8 1266 are positioned alternately inside the ventilation 9 lumen of the endotracheal tube 1252. The suction catheter or the nebulizing catheter can be withdrawn 11 temporarily and maintained in its sterile sheath while 12 the other is being used.
13 Referring to FIG. 72 there is another 14 arrangement for connecting a suction catheter and nebulizing catheter to an endotracheal tube. In this 16 embodiment, a manifold 1270 connects to the proximal end 17 of the endotracheal tube 1252. The manifold 1270 has 18 port 1274 for receiving the nebulizing catheter 1266 and 19 a second port 1276. A distal manifold 1278 of a suction catheter 1280 connects to the second port 1276. The 21 suction catheter manifold 1278 has a port 1282 for 22 connecting to the ventilator. This arrangement can be 23 used similarly to the arrangement of FIG. 71.
24 FIG. 73 shows still another arrangement for connecting a suction catheter and a nebulizing catheter 26 to an endotracheal tube. In this embodiment, the 27 endotracheal tube 1252 is provided with a proximal end 28 that includes dual ports. A first port 1284 receives the 29 nebulizing catheter 1266. The second port 1286 may be connected to either directly to a ventilator or may be 31 connected to a distal end of a suction catheter (not 32 shown) in a conventional manner.
33 In another alternative embodiment (not shown), 34 the nebulizing catheter could be positioned down the suction lumen of the suction catheter.
36 FIG. 74 shows another embodiment of a suction 37 catheter also incorporating a nebulization of an aerosol.

2152002.

1 In FIG. 74; a suction catheter 1400 is extends from the 2 ventilation lumen of an endotracheal tube 1250. The 3 suction catheter 1400 includes distal suction orifices 4 1402 located close to the distal end of the suction catheter shaft. Located along the suction catheter shaft 6 proximally of the suction orifices 1402 are one or more 7 pairs of liquid and gas orifices 1404. The liquid and 8 gas orifice pairs 1404 are located with respect to each 9 other to produce an aerosol of the liquid being delivered to the liquid orifice as in the previous embodiments.
11 The nebulization orifices 1404 are oriented radially from 12 the suction catheter shaft to direct the aerosol 13 delivered from the nebulization orifices 1404 toward the 14 airway passage wall. In one embodiment, the aerosol being delivered is a mucolytic agent. The suction 16 provided by the suction orifices draws the mucolytic 17 agent delivered from the nebulization orifices as well as 18 mucous treated by the mucolytic agent in a distal 19 direction into the suction orifices 1402.
Another embodiment of the suction catheter with 21 aerosol delivery is shown in FIG. 75. A suction catheter 22 1410 is located in a ventilation lumen of the 23 endotracheal tube 1250. As in the previous embodiment, 24 the suction catheter 1410 has a distal suction orifice 1412 for removing mucous from the airway passage. In 26 addition, the suction catheter 1410 also includes distal 27 gas and liquid orifices 1414 located in proximity to each 28 other to produce a aerosol. The liquid and gas orifices 29 are located in a distal extension 1416 of the suction catheter shaft so that they are distal of the suction 31 orifice 1412. The liquid and gas nebulization orifices 32 1414 are oriented in a proximal direction toward the 33 suction orifice 1412. The distal extension 1416 is 34 formed to bring the nebulization orifices 1414 close to the wall of airway passage so that the aerosol delivered 36 from the nebulization orifices 1414 washes the airway 37 passage wall. As in the previous embodiment, the aerosol 1 delivered may be a mucolytic agent to facilitate 2 suctioning of the mucous out of the airway passage. The 3 pressurized gas flow may be used to contribute to the 4 dislodgement of mucous from the airway passage walls.
F. Nebulization with Vibration 6 A vibrating orifice, a screen with multiple 7 orifices or perforations, or a vibrating wire located at 8 the distal tip of the nebulizing catheter may also be 9 employed to assist in the generation of fine aerosol particles. The vibration may be generated by 11 electromechanical, hydraulic, pneumatic, or piezoelectric 12 means. The vibrations may be generated at the tip of the 13 catheter, in the shaft, or extracorporeally.
14 One embodiment of a nebulizing catheter incorporating a vibrating tip is shown in FIG. 76. A
16 nebulizing catheter 1300 includes a shaft 1302 through 17 which extend a lumen 1304 for the delivery of a liquid 18 medicine and a lumen 1306 for the delivery of a 19 pressurized gas. The liquid lumen 1304 communicates with a distal liquid orifice 1308 and the gas lumen 1306 21 communicates with a distal gas orifice 1310 located at a 22 distal end of the nebulizing catheter shaft. At the tip 23 the orifices 1308 and 1310 may be drilled or formed in a 24 piezoelectric material 1314 or may be drilled or formed in an orifice insert, plate, tube or screen mechanically 26 attached to the tip such that the vibrations of the 27 material are transferred to orifices. Although both the 28 gas and liquid orifices may be vibrated, alternatively 29 only the liquid orifice may be vibrated. In still a further embodiment, the entire shaft of the catheter may 31 be vibrated so that the vibrations are transferred to the 32 tip. The vibrations may be amplified by mechanical means 33 to increase the amplitude of the orifice oscillation.
34 Two electrical lead wires 1316 and 1318 may be used to conduct bipolar or unipolar pulses from an extracorporeal 36 generator and control circuit to the piezoelectric 21520o2 1 material 1314. The amplitude and frequency of the 2 orifice vibrations may be adjusted to optimize aerosol 3 production based on the gas and solution flow rates, the 4 orifice configuration, and the desired size of the aerosol particles. The generation device would be 6 provided with a current leakage sensor to terminate its 7 operation in the event it detects current leakage in the 8 system. The vibrations can be pulsed to coincide with 9 inspiration and also to control heat generated by vibration at the tip. One or more gas supply lumens and 11 orifices at the catheter tip can be used to assist in the 12 dispersion and transport of the particles produced at the 13 vibrating orifice.
14 In a further alternative embodiment, the orifice may be vibrated by means of a vibrating wire 16 connected to the orifice that is caused to vibrate from a 17 generator connected to the proximal end. In still a 18 further embodiment, a vibrating wire, similar to the wire 19 tip shown in FIGS. 16-19, may extend distally past a non-vibrating orifice to cause aerosolization of a liquid 21 delivered from the orifice that impinges onto the 22 vibrating wire. In a still further embodiment, the tip 23 may be vibrated remotely, e.g. from a source outside the 24 body, by means of a magnetic field.
A liquid supply to the catheter tip can also be 26 rapidly pulsed to cause small droplets to be ejected at 27 the solution orifice. This may cause a finer aerosol to 28 be developed than by feeding a continuous stream of 29 solution to the orifice. The pulsation can be accomplished by rapidly expanding and contracting all or 31 part of the solution reservoir (including the lumen).
32 The expansion and contraction of the reservoir can be 33 caused by electromechanical, hydraulic, pneumatic, or 34 piezoelectric actuators forming the reservoir, within the reservoir or moving flexible portions of the reservoir.
36 Such an embodiment is shown in FIG. 76. A nebulizing 37 catheter 1500 includes a shaft 1502 having a gas lumen 1 1502 connected to a source of pressurized gas 1504 and a 2 liquid medicine lumen 1506 connected to a source of 3 liquid medicine 1508. Included in the liquid medicine 4 source 1508 is a means for imparting compression waves or pulsation into the liquid. The waves are indicated in 6 the liquid at 1509. The wave imparting means may be a 7 transducer 1510 or other similar device. The vibration 8 inducing device 1510 may be driven by a frequency 9 generator 1513 at a frequency greater than 100 hertz.
The vibrations induced in the liquid may be focussed or 11 directed toward the distal liquid orifice 1514.
12 In the case where the vibrations are generated 13 at a location proximal of the tip, the nebulizing 14 catheter shaft may incorporate a mechanical means in the shaft or near the orifices capable of transmitting or 16 amplifying the pulsations. In the embodiment of FIG. 77, 17 a wire 1516 may extend from the pulsation generating 18 means 1510 into the liquid lumen 1506 to help convey the 19 vibrations 1509 to the distal orifice 1514. The pulsations imparted to the liquid may be used to generate 21 an aerosol from the distal liquid orifice 1514 or 22 alternatively may be used in conjunction with the 23 pressurized gas delivered through the gas lumen 1502 for 24 enhanced aerosolization. The amplitude and frequency of the orifice vibrations may be adjusted to optimize 26 aerosol production based on the gas and solution flow 27 rates, the orifice configuration, and the desired size of 28 the aerosol particles.
29 The volume dispersed from the liquid orifice 1514 by each pulse should be less than approximately 10 31 microliters and the pulsation should occur at a frequency 32 greater than 100 Hertz, although smaller volumes and 33 faster frequencies may be used to produce a finer 34 aerosol. It is preferable that the reservoir and lumens be constructed or a material of minimal compliance to 36 ensure minimal attenuation of the pulsation. The gas 37 supply orifice at the catheter tip can be used to assist 1 in the dispersion and transport of the particles produced 2 at the solution orifice. These micro pulsations can be 3 incorporated into a series with pauses between them to 4 coincide with the patient's inspiratory phase.

G. Other Method for Aerosol Generation 6 The above embodiments describe a nebulization 7 catheter in which an aerosol is generated by directing a 8 pressurized gas through a catheter near an orifice from 9 which the liquid to be nebulized exits. It is considered to be within the scope of the invention described herein 11 to use other means or agents to generate an aerosol for 12 delivery of a medication to the respiratory tract. For 13 example, the above embodiments may be used in conjunction 14 with devices that utilize other means to generate an aerosol of a liquid medication. A liquid delivered by a 16 single liquid lumen may be nebulized by applying 17 ultrasonic energy to the liquid, electrospray, steam, or 18 a micropump similar to those used in ink jet type 19 printers. These alternative approaches to nebulization may be substituted for the use of a pressurized gas for 21 some of the embodiments described above, or may be 22 combined with pressurized gas or with each other to 23 produce an aerosol of the liquid medication.
24 The nebulization catheter embodiments described herein could also be used in other types of nebulizers 26 that are used externally of a patient's respiratory 27 system, such as small volume nebulizers (SVN), 28 humidification nebulizers, or nebulizers used for ocular 29 or nasal drug administration. When used in such other types of nebulizers, the embodiments of the nebulization 31 catheter disclosed herein provide for a fine aerosol 32 without the potential disadvantages of impacting the 33 liquid on a baffle or recirculating the liquid medicine 34 on a continuous basis which are common in such nebulizers.

2( S2-C.~, oz 1 It is intended that the foregoing detailed description be regarded as 2 illustrative rather than limiting and that it is understood that the following claims 3 including all equivalents are intended to define the scope of the invention.

Claims

1. A catheter for delivering an aerosol of medicine to a patient comprising:

a catheter shaft;

a liquid lumen centrally located in said shaft and adapted for conveying a medicine in liquid form;

a plurality of gas lumens peripherally located around said liquid lumen and adapted for conveying a gas;
a distal liquid orifice communicating with said liquid lumen; and a plurality of distal gas orifices communicating with said plurality of gas lumens, said plurality of distal gas orifices being aligned with respect to said distal liquid orifice so as to nebulize a liquid medicine discharged from the liquid orifice.

2. The catheter of claim 1 wherein at least a portion of said shaft surrounding said liquid lumen is formed of a low compliance material so that flow control at said distal liquid orifice of a fluid delivered through said liquid lumen is more responsive to flow control at a location proximal thereto.

3. The catheter of claim 1 further comprising a tip formed by a taper in the distal end of the catheter.

4. The catheter of claim 3, wherein the distal end of the catheter comprises a tip region that is tapered such that the lumens are in closer proximity to each other at a distal end of the tip region than at a proximal end of the tip region.

5. The catheter of claim 4 wherein a respective internal diameter of the lumens is smaller at a distal end of the tip than at a proximal end of the tip.

6. The catheter of claim 3, wherein six said gas orifices surround said liquid orifice and six said gas lumens are congruent with the six gas orifices.

7. The catheter of claim 3, wherein the liquid orifice has a diameter of 0.002 inches.

8. The catheter of claim 3, wherein each gas orifice has a diameter of 0.002 inches.

9. The catheter of claim 1, wherein the catheter further comprises:

a proximal shaft section and a distal shaft section; and a plurality of lumens in said proximal shaft section wherein the plurality of lumens comprise the liquid lumen and the plurality of gas lumens.

10. The catheter of claim 9 wherein said liquid lumen is a central lumen and said gas lumens are non-centered.

11. The catheter of claim 10 further comprising:

a distal end of the proximal shaft section connected to the proximal end of the distal shaft section;

a tapered cavity formed between said distal end of said distal shaft section and said distal end of said proximal shaft section;

a distal orifice located at the distal end of the distal shaft section; and a tubular extension extending the central lumen used to convey a liquid through the tapered cavity and out said distal orifice; and wherein said distal orifice is sized to permit gas flow in an annular region around the tubular extension to nebulize the liquid that exits the distal orifice of the tubular extension.

12. The catheter of claim 11, wherein the distal orifice has an interior diameter of 0.25 inches.

13. The catheter of claim 11, wherein the tubular extension has an outer diameter of 0.012 inches and an inner diameter of 0.007 inches.

14. The catheter of claim 9 wherein the distal shaft section is composed of stainless steel.

15. The catheter of claim 1, comprising a tapered wire located with respect to the liquid orifice so that liquid from the liquid lumen continues to flow distally of the distal liquid orifice along the wire.

16. The catheter of claim 15, wherein the wire has a curved shape such that gas from the gas orifices causes the wire to whip round in a spiral motion.

17. The catheter of claim 1 further comprising:
a porous plug located in said liquid orifice.

18. The catheter of claim 1 further comprising:

means for increasing the width of the aerosol.

19. The catheter of claim 18, wherein the means for increasing width comprises a tapered wire.

20. The catheter of claim 1, further comprising a peripherally located lumen which is used for sensing purposes.

21. The catheter of claim 1 further comprising a safety stop on a proximal portion of the catheter shaft.

22. The catheter of claim 1 further comprising:

graduated markings on said catheter shaft.

23. The catheter of claim 1 further comprising:
luer lock connectors on proximal ports communicating with said gas lumens and said liquid lumen.

24. The catheter of claim 1 further comprising:

a stripe on said catheter shaft.

25. The catheter of claim 1, wherein said catheter shaft comprises:

a further lumen extending therethrough; and a fiber optic scope extending through said further lumen.

26. A method of forming a catheter for nebulizing a liquid with a gas, the catheter having closely spaced distal orifices comprising:

providing a multilumen extruded polymer tubing;
heating a portion of the tubing to a transition temperature of the tubing;

forming a j-shaped distal section in the multilumen extruded polymer tubing, wherein the multilumen extruded polymer tubing curves away from a longitudinal axis of the catheter at a distal end of the catheter; and forming a plurality of orifices at the distal section, the plurality of orifices being sized to nebulize a liquid delivered through one of the lumens to form an aerosol with a gas delivered through another of the lumens.

27. The method of claim 26, wherein the step of forming a plurality of orifices further comprises:

cutting a distal end of the distal section.

28. The method of claim 26, further comprising:
cutting the tubing to size to form a shaft portion of the catheter.

29. The method of claim 26, further comprising:
exposing a portion of the tubing to high energy radiation.

30. The method of claim 26, in which the catheter is for use in the respiratory system.

31. The method of claim 26, in which the step of heating further comprises:

heating the tubing to a temperature between a melt state and a glass state of the tubing.

32. The method of claim 26, further comprising providing radiopaque markings along at least a portion of the catheter.

33. The method of claim 32, wherein the radiopaque markings comprise graduated markings along the catheter.

34. The method of claim 32, wherein the step of providing radiopaque markings comprises attaching at least one of radiopaque bands of metal and radiopaque heat shrunk bands of doped radiopaque plastic to the catheter.

35. The method of claim 26, further comprising providing ultrasonically reflecting markings along the catheter.

36. The method of claim 26, further comprising fabricating a stripe along a side of the catheter, wherein the strip comprises one of a radiopaque material or an ultrasonically reflective material, whereby the stripe is useful for determining a rotational orientation of the catheter.

37. The method of claim 36, wherein fabricating a stripe comprises forming the stripe with a coextrusion process.

38. The method of claim 36, wherein fabricating a stripe comprises embedding a wire in a wall of the nebulization catheter.

39. The method of claim 26, wherein at least a portion of the catheter is constructed of a compliant material.

40. The method of claim 26, wherein the j-shaped distal section is maintained in an orientation having the plurality of orifices pointing substantially towards a proximal end of the catheter.

41. The method of claim 40, wherein the j-shaped distal section is maintained in the orientation by attaching a first end of a tether to an end of the j-shaped distal section and a second end of a tether to a portion of a shaft of the catheter.

42. The method of claim 41, wherein the tether comprises a wire.

43. The method of claim 26, wherein at least a portion of the catheter is constructed of a compliant material.