Intermittent signal actuated nebulizer synchronized to operate in the exhalation phase, and its method of use

A self-contained, high capacity nebulizer, having automatic mixing and temperature control features is provided, and its method of use. The nebulizer is designed for use in conjunction with mechanical respirators, ventilators, or breathing machines, and for this purpose will use electrical signals generated by or received from the respirator to automatically control and synchronize the nebulizing and mixing functions such that nebulization occurs only during the exhalation phase of the respiratory function to load the gas passageway of the respirator to the patient with a standardized dose of medicinal aerosol. Upon commencement of the inhalation phase, the aerosol in the gas passageway is ventilated into the lungs of the patient to which it is attached.

TECHNICAL FIELD 
The present invention relates to nebulizers for creating medicinal aerosols 
for inhalation therapy. In particular, the present invention relates to 
nebulizers used during the exhalation phase of the breathing cycle in 
conjunction with and without interfering with mechanical breathing 
machines which are used to ventilate the lungs of patients who cannot 
breathe unaided. 
BACKGROUND ART 
The thin membrane of the lungs provides an easily penetrated, convenient 
and generally safe means for obtaining rapid absorption of medication by 
the body. This is especially desirable where the lungs themselves are 
diseased or injured. Such medication or drugs are generally delivered to 
the lung membrane in the form of a fine mist or aerosol which is breathed 
into the lungs through the nose or mouth of the patient. A variety of 
devices, called nebulizers by those skilled in the art, have been 
developed for converting liquids into fine aerosols for this purpose. The 
simplest of these devices is the hand-held atomizer which converts a 
liquid to an aerosol when a bulb is compressed to produce a jet of air 
which atomizes the medication and propels it out of the atomizer. To be 
effective, the aerosols need to be provided at high concentrations and 
with droplet size in the respirable range (mass median aerodynamic 
diameter less than 3 micrometers). 
Nebulizers are particularly useful for initiating and continuing 
respiratory therapy in conjunction with respirators, mechanical 
ventilators or breathing machines (hereinafter referred to generically as 
respirators) used to ventilate the lungs of patients having serious 
respiratory impairment. While some respirators incorporate nebulizers in 
their design, many do not. Nebulizers incorporated into the structure of 
such respirators often suffer from many disadvantages. One such 
disadvantage is severely limited capacity for medication to be nebulized, 
requiring frequent interruptions in the therapy as new medication is added 
to the nebulizer reservoir. 
Most, if not all, such nebulizers are incorporated in respirators in which 
the inhalation and exhalation phases of the breathing cycle are triggered 
by changes in air pressure caused by the patient himself. Such "demand" 
respirators are not useful for patients whose respiratory systems are 
paralyzed and incapable of causing even slight changes in air pressure. 
These patients are aided by mechanical respirators in which the phases of 
the breathing cycle are triggered by electrical signals. There is now no 
effective means for patients on such respirators to receive aerosol 
treatment. 
Thus, the need exists for a nebulizer which can be attached to a mechanical 
respirator, especially those in which the breathing cycle is controlled by 
an electrical signal, which has a reservoir capacity sufficient to enable 
several hours of continuous treatment, which can prevent the settling of 
suspensions or mixtures without creating nebulization-destroying 
turbulence. 
U.S. Pat. No. 4,832,012 discloses the principal of signal actuated 
synchronization of nebulization for delivery of aerosolized medicine to 
patients whose breathing is supported or augmented by a mechanical 
respiratory. In that reference, nebulization could be effected during 
inhalation or exhalation, but the primary trust of that reference was to 
provide aerosols during the inhalation phase of the breathing cycle to mix 
with the inhalation tidal volume provided by the respirator, and in 
synchrony with the normal operation of the respiratory. However, it has 
been found that the addition of volume of gas to mix with the inhalation 
tidal volume provided by the respirator, may interfere with the normal 
operation of the respirator in certain operating modes, and the medicinal 
aerosol is diluted by the portion of gas delivered by the respirator. 
SUMMARY OF THE INVENTION 
The present invention is based upon the nebulization of medicine during and 
synchronized with the exhalation portion of each breath of the breathing 
cycle to fill the airline leading from the nebulizer to the patient with a 
standardized dose of medicinal aerosols that are delivered to the lung by 
the force of the flow of breathing gas (oxygen-enriched air) delivered by 
the respirator during the inhalation portion of the breathing cycle. One 
advantage of this invention is that more concentrated standardized dose of 
aerosol is delivered to the patient with the first parcel of gas that 
enters the lungs for each breath during the inhalation process. In 
addition, the signal used to actuate the nebulizer may be obtained from 
the ventilator or from an independently generated signal established by 
the nebulization system utilizing the readily detected respiratory air 
line pressure or pressure drop across filter from exhaled gas flow. Also, 
certain safety monitoring features are incorporated into such a system to 
detect aerosol clogging of respiratory filters and prevent interference 
with the normal operation of the respirator. 
The nebulization system of the present invention can be attached to or 
operated with a mechanical respirator utilizing either a breathing cycle 
electrical signal obtained from the respiratory or an independent 
electrical signal generated by the nebulizer system which detects and 
responds to the exhalation initiation of the respirator. Such a 
synchronized signal actuated nebulizer system is designed to operate 
during the exhalation phase of the breathing cycle while treating a sick 
patient and efficiently providing, in the short time available, a 
medicinal aerosol in the appropriate and desired volume, concentration, 
and particle size distribution for deposition in the respiratory airways 
of the lungs. An important feature of such a system is that all of the 
aerosol is generated quickly (in about 1 second or less) and in a way that 
does not interfere with the control system of the respirator. The 
nebulizer system has a reservoir of capacity sufficient to enable several 
hours of continuous treatment and with provision to prevent the settling 
of suspensions or mixtures without creating nebulization-destroying 
turbulence, and provides a precisely measured volume of medicinal aerosol 
generated during patient exhalation in a manner to reach the patient at 
the precise moment when inhalation begins. 
In one embodiment, the present invention provides a nebulizer for use with 
mechanical respirators which use electrical signals to control the 
breathing cycle. The nebulizer of this embodiment uses the existing 
electrical signals from the mechanical respirator to synchronize aerosol 
generation to fill the gas passageway from the respirator to the patient 
during the exhalation cycle. Upon the initiation of the inhalation cycle, 
the aerosol is delivered from the gas passageway to the patient. 
Nebulization is obtained in this embodiment using the premixed 
oxygen-enriched air provided at high pressure to the respirator. Automatic 
temperature regulation and stirring of the liquid medication is optionally 
provided to preclude concentration change, separation or settling of the 
medication. Finally, a large volume reservoir is provided to eliminate the 
need for refilling during lengthy treatment protocols.

DETAILED DESCRIPTION OF THE INVENTION 
FIG. 1 shows a nebulizer apparatus 10 of the present invention operably 
connected to a mechanical respirator 70. The nebulizer apparatus 10 
comprises, in a housing, compressed gas inlet 2, at one end of a 
compressed gas conduit 4, adapted to be connected to a compressed gas 
source at pressure indicated by gauge 5. Preferably this compressed gas 
source is the same source which is furnishing oxygen-enriched air to the 
respirator 70, and provides compressed air or oxygen mixture to the 
nebulizer ranging up to about 50 psig. 
Compressed gas conduit 4 is connected at the other end to a first 
electrically operated nebulizer valve 7, and a plurality of second 
electrically operated nebulizer valves 6, all of which are substantially 
similar. Examples of such valves which have been found useful include the 
Honeywell Skinner K4M ultraminiature 4-way solenoid operated pneumatic 
valve and Numatics HS series 2-way solenoid operated valves. Three valves 
6 are shown in FIG. 1. 
Nebulizer valves 6 and 7 are connected by a plurality of electrical lead 
wires 8 to a microprocessor 9 and are controlled by the microprocessor 9. 
The microprocessor 9 receives the signals from a signal source 72 on the 
respirator 70 which controls the inhalation/exhalation phase of the 
breathing cycle. The microprocessor 9 controls the valves 6 and 7 to 
provide for a safe and effective operation. Examples of signal source 72 
include a respirator solenoid, such as a solenoid actuated inhalation 
valve, an external electronic monitoring system, or an electronic 
interface attached to a signal generator on respirator 70, such as an 
interface connected to a logic circuit in the respirator. 
A control unit 80, whose control panel is shown in FIG. 2, is connected to 
the microprocessor 9. The control unit 80 controls the functions of the 
nebulizing apparatus 10 of the present invention. 
Each of the nebulizer valves 6 connects the compressed gas source 4 to 
nebulizer conduits 12 leading to aerosol nozzles 22. Each nebulizer valve 
6 switches between two positions as electrical on/off signals are 
received. In the first position, during the exhalation phase of the 
respirator 70 when the electric signal is "on", a passageway is opened 
between compressed gas conduit 4 and nebulizer conduits 12 and remain open 
until the desired aerosol volume has generated or until the inhalation 
phase is initiated by the respiratory 70 as controlled by microprocessor 
9. In the second position, when the electric signal is "off", the 
nebulizer conduits 12 are sealed off. 
Nebulizer conduits 12 are attached at their other ends to aerosol nozzles 
22, which include liquid feed tubes 24 extending into reservoir 26. 
Reservoir 26 includes magnetic stirring bar 28 which is located in the 
bottom of the reservoir. The liquid medicine contained in reservoir 26 is 
preferably kept at constant temperature by a reservoir heater or cooler 
34. 
A chamber 14 houses an AC motor 11 which rotates a cooling fan 13 and a 
magnet 18. The rotation of the magnet 18 causes the stir bar 28 to rotate 
to prevent sedimentation or separation of medicinal constituents. 
The liquid medicine in the reservoir 26 is drawn via the liquid feed tubes 
24 and is converted by the aerosol nozzles 22 into an aerosol having 
droplets with a mass median aerodynamic diameter less than about 3 micron. 
The aerosol is generated into the air space 25 above the reservoir 26. The 
aerosol generated in the air space 25 enters into an aerosol tube 31. 
The temperature of the aerosol in the aerosol tube 31 is controlled by a 
temperature controller 33. In one embodiment, the temperature controller 
is simply an electric heater having a control unit. Within the aerosol 
tube 31 is also a neb-flow sensor 35. The neb-flow sensor 35 detects the 
amount of aerosol being delivered through the aerosol tube 31. The output 
of the neb-flow sensor 35 is supplied as a signal to the microprocessor 9 
via neb-flow sensor pressure/vacuum lines 17. 
The respirator 70 has an inhalation tube 71 and an exhalation tube 73. The 
inhalation tube 71 fluidically connects the respirator 70 to a patient and 
during the inhalation phase, breathing gas is supplied from the respirator 
70 along the inhalation tube 71 into the respiratory tract of the patient. 
The aerosol tube 31 connects the air space 25 above the liquid 26 to the 
inhalation tube 71 at a nebulizer input 30. In addition, a pop-off valve 
13 is also located in the inhalation tube 71. The function of the pop-off 
valve 13 is to relieve any pressure which is generated to dangerous levels 
within the inhalation tube 71. It functions purely as an emergency safety 
valve. Finally, an airway pressure sensor 15 is also positioned in the 
inhalation tube 71. The airway pressure sensor 15 generates a signal which 
is also supplied to the microprocessor 9 via airway pressure monitoring 
line 16. A humidifier 37 whose output is water vapor mixed with the 
breathing gas is also connected to the inhalation tube 71. 
The exhalation tube 73 fluidically connects the patient to the respirator 
70. Located within the exhalation tube 73 is an exhalation filter 75. 
Upstream from the exhalation filter 75, i.e., between the exhalation 
filter 75 and the patient is an upstream filter pressure sensor 77. 
Downstream from the exhalation filter 75, i.e., between the exhalation 
filter 75 and the ventilator 70 is a downstream filter pressure sensor 79. 
The upstream filter pressure sensor 77 and the downstream filter pressure 
sensor 79 each provide a signal which is supplied to the microprocessor 9. 
The solenoid 7 is also connected to receive gas from the gas conduit 4 and 
is adapted to supply gas to a decay flow line 11 to the exhalation tube 
73, upstream from the upstream filter pressure sensor 77. Thus, the 
solenoid 7, when activated, provides a stream of compressed gas which is 
supplied into the exhalation tube 73, between the patient and the upstream 
filter pressure sensor 77. The function of the decay solenoid 7 is also 
controlled by the microprocessor 9. 
The operation of the nebulizer apparatus 10 of the present invention will 
be understood as follows. The practitioner first determines the amount of 
volume per breath of the standardized dose of aerosol which is to be 
generated by the apparatus 10 of the present invention which is to be 
supplied to the inhalation tube 71. The amount is entered on the control 
unit 80. The microprocessor 9 receives the signal and based upon its 
knowledge of the gas pressure from the compressed gas conduit 4, and the 
cross-sectional area of each of nebulizing nozzles 22, the microprocessor 
9 calculates the amount of time which the solenoids 6 would have to be 
activated in order to introduce the desired amount of aerosol into the 
inhalation tube 71. Alternatively, the signal from the neb-flow sensor 35 
is used by the microprocessor 9 to turn off the nebulizer solenoids 6 when 
the desired charging volume has been generated. 
When the mechanical respirator 70 begins the exhalation phase of the 
respiratory cycle, electrical signal 72 supplies the signal to the 
microprocessor 9. (As will be discussed hereinafter, a number of other 
signals are supplied to the microprocessor 9 to indicate the beginning of 
the exhalation cycle. These additional signals are used in the event the 
ventilator 70 cannot provide the electrical signal source 72 or is used as 
a safety backup to the electrical signal source 72.) When the mechanical 
respirator 70 begins the exhalation phase, the inhalation port 76 is 
closed. The exhalation port 74 is opened, opening the exhalation tube 73. 
After the electrical signal source 72 generates the signal indicating the 
beginning of the exhalation phase, the microprocessor 9 activates the 
solenoids 6 to the three nebulizing nozzles 24. Thus, after the 
commencement of the exhalation phase, and after the detection of the 
electrical signal, maximum generation of the aerosol from the apparatus 10 
commences and continues until the standardized volume or dose of aerosol 
has been generated. Compressed gas flows through the compressed gas 
conduit 4 into the three nebulizer conduits 12 and into the nozzles 22, 
which draw liquid via liquid feed tubes 24 from the liquid reservoir 26. 
The aerosol is then generated and is supplied into the air space 25 above 
the reservoir 26. The aerosol generated in the air space 25 then enters 
into the aerosol tube 31 where the temperature thereof is controlled by 
the temperature controller 33. The aerosol then leaves the aerosol tube 31 
and enters into the inhalation tube 71 through port 30. Generation of the 
standardized dose of aerosol fills the charging volume space 40 between 
the nebulizer input port 32 and the patient 41 in the inhalation tube 71. 
Any excessive aerosol will enter the exhalation tube 73 and return to the 
respirator 70. 
During the exhalation phase, the pressure in the inhalation tube 71 is 
monitored by the airway pressure sensor 15 and is supplied to the 
microprocessor 9. This provides a safety signal to the microprocessor 9 to 
shut off the function of the aerosolization in the event pressure within 
the inhalation tube 71 builds to an excessive level or if inhalation 
begins. In addition, a mechanical safety pop-off valve 13 is provided 
wherein in the event the pressure in the inhalation tube 71 exceeds the 
pressure regulation of the pop-off valve 13, the valve 13 would 
automatically open relieving the pressure in the inhalation tube 71. 
During the exhalation cycle, the respirator 70 continuously monitors the 
pressure on the exhalation tube 73. In order to provide for a smooth decay 
flow of gas entering into the exhalation tube 73 from the patient, and 
thereby simulating smooth exhalation reduction from the patient, the 
solenoid 7 is activated during the exhalation cycle. When the solenoid 7 
is activated, the gas from the compressed gas conduit 4 fills a fixed 
volume chamber 82. The fixed volume chamber 82 has a calibrated orifice 
which is connected to the decay flow line 11 and is supplied to the 
exhalation tube 73. During the time period in which the aerosol is being 
generated, the fixed volume chamber 82 is filled with breathing gas to a 
predetermined pressure. At the end of the charging period, the compressed 
gas from the gas conduit 4 is turned off. The gas from the fixed volume 
chamber 82 is then allowed to flow in a decay manner into the exhalation 
tube through the orifice connecting the chamber 82 to the decay flow line 
11. When the pressure in the fixed chamber 82 gradually reduces, the flow 
entering the decay flow line 11 simulates a natural first order decay. 
Synchronous with the beginning of the exhalation cycle, the three 
nebulizing nozzles 22 are turned on simultaneously or one at a time to 
produce the desired charging volume during a portion of the exhalation 
period to allow the respirator 70 to maintain and/or support the patient's 
spontaneous breathing effort without interference from the charging flow. 
When the respirator 70 begins the inhalation phase of the respiratory 
cycle, the electrical signal source 72 switches to an "off" position. In 
the "off" position, the respirator inhalation port 76 opens; the 
respirator exhalation port 74 is closed. 
The solenoid valves 6 are controlled by microprocessor 9 when first, the 
desired standardized dose is reached (usually only takes portion of the 
exhalation phase), or secondly when microprocessor 9 detects the 
electrical signal source 72 turn to an "off" position. In the first 
priority, the solenoids 6 can be turned off one at a time. In the second 
case, the solenoids 6 are turned off immediately to allow respirator 70 to 
begin the inhalation phase. 
The gradual turning off of the plurality of solenoids 6 generates a gradual 
pressure reduction and flow shaping that prevents spurious triggering of 
the respiratory ventilator 70 caused by rapid flow changes. Because the 
aerosol generated by the apparatus 10 of the present invention fills the 
inhalation tube 71 between the nebulizer input 30 and the patient with the 
desired standardized volume or aerosol dose, when the ventilator 70 begins 
the inhalation phase and pushes the gas in the inhalation tube 71 into the 
respiratory tract of the patient, the aerosol in the charging volume space 
40 would be the first gas pushed into the lungs of the patient. Thus, the 
medicine produced by the aerosol would be first delivered to the patient 
during the inhalation cycle. 
The advantage of the apparatus 10 and method of the present invention is 
that generating the aerosol and introducing it into the charging volume 
space 40 during the exhalation phase means the aerosol is pre-charged in 
the inhalation tube. Further, the amount of aerosol in the charging volume 
space 40 can be metered or controlled by the microprocessor 9. In 
addition, the introduction of aerosol during the exhalation phase does not 
perturb the pressure of the gas from the respirator 70 delivered during 
the inhalation phase. 
As previously discussed, the source of electrical signal 72 may not be 
provided by all ventilators 70. The upstream filter sensor 77 and the 
downstream filter sensor 79 each provides a signal via the exhalation 
filter sensor pressure/vacuum lines 19, the difference of which indicates 
the commencement of the exhalation phase. Thus, upon the immediate 
commencement of the exhalation phase, a pressure differential would be 
detected between the upstream filter sensor 77 and the downstream filter 
sensor 79, respectively. This pressure differential, supplied as a signal 
to the microprocessor 9, would indicate to the microprocessor 9 that the 
exhalation cycle has commenced. This signal can be used by microprocessor 
9 to begin nebulization when no respirator electrical signal is available. 
Alternatively, the airway pressure sensor 15 supplies a signal to the 
microprocessor 9 indicating the beginning of the exhalation and also the 
beginning of the inhalation for control of the nebulization by 
microprocessor 9 when no respirator electrical signal is available. 
In addition, there are many safety considerations with the apparatus 10 of 
the present invention. With the upstream and downstream filter sensor 77 
and 79 respectively having an exhalation filter 75 therebetween, the 
condition of the exhalation filter 75 can be continuously checked. As the 
apparatus 10 of the present invention is continuously used, and as the 
filter 75 becomes increasingly clogged, the pressure differential between 
the upstream filter sensor 77 and the downstream filter sensor 79 would 
increase. Alternatively, the loading/clogging of the exhalation filter can 
be detected using the airway pressure sensor 15 which supplies a signal to 
microprocessor 9 via line 16. This is because airway pressure during 
nebulization is a function of the resistance of the exhalation filter. The 
filter loading/clogging can be detected by the microprocessor 9 and can be 
signaled on the control unit 80 as an alarm that the exhalation filter 75 
needs to be examined and/or changed. 
As previously discussed, the airway pressure sensor 15 provides an 
independent airway pressure measurement upstream to exhalation filter to 
monitor the patients safety. Finally, the control unit 80 can control the 
apparatus 10 to cause it to pause its operation. This provides an 
independent check on the respirator system 70. The control unit shown in 
FIG. 2 provides for setting of charging volume, respirator selection (for 
different commercial respirators), heater temperature, nebulizer hold 
option, alarm test option, alarm reset, and alarm silence. Further, the 
control unit displays respirator selection, charging volume, alarm, 
warning, and caution, indication of exhalation filter loading, patient 
peak inspiratory pressure, heater temperature and nozzle gas pressure. 
Signals from the neb-flow sensor 35 are used to alarm if either inadequate 
charging volume is generated or if the nebulizer nozzle 24 malfunction in 
the "on" position. The microprocessor 9 provides yet additional safe and 
effective operation for the apparatus 10 of the present invention. In the 
preferred embodiment, the microprocessor 9 is an Intel 8751 available from 
Intel Corporation. A copy of the program, written in the assembly 
language, for execution by the microprocessor 9 is attached as Exhibit A.