WO2020236860A1

WO2020236860A1 - Mechanical ventilation circuit with wet nebulization

Info

Publication number: WO2020236860A1
Application number: PCT/US2020/033684
Authority: WO
Inventors: Gerald Smaldone
Original assignee: The Research Foundation For The State University Of New York
Priority date: 2019-05-21
Filing date: 2020-05-20
Publication date: 2020-11-26

Abstract

A ventilator circuit apparatus is provided for the administration of an aerosolized drug from a nebulizer through an endotracheal tube to a patient on a medical ventilator, wherein a humidifier is provided that delivers humidified breathing gases to the nebulizer. The apparatus includes a T-fitting and two-way selector valve that permits the breathing gases to bypass the nebulizer, or to flow through the nebulizer. In embodiment, the nebulizer is breath-enhanced and breath actuated.

Description

MECHANICAL VENTILATION CIRCUIT WITH WET NEBULIZATION

CROSS REFERENCE TO RELATED APPLICATION

[0001] This patent application claims priority to US Patent Application 62/850,728 filed May 21 , 2019, the contents of which are incorporated by reference.

FIELD OF THE INVENTION

[0002] A ventilation circuit is disclosed for use on an intubated patient with a first and second T- fitting and a breath-enhanced and breath actuated nebulizer. The nebulizer can be removed without interrupting the flow of breathing gases to the patient. In an embodiment, a humidifier is provided that delivers humidified breathing gases to the nebulizer. In an alternative

embodiment, a heat and moisture exchanger provides humidified breathing gases to the patient.

BACKGROUND

[0003] Positive pressure mechanical ventilation with an endotracheal tube is an important therapeutic modality for patients who are unable to spontaneously breathe on their own, or unable to breathe efficiently, due to impaired lung function. Positive pressure mechanical ventilation conventionally uses a computer controlled breathing apparatus that regulates airflow to and from the patient. Patients requiring mechanical ventilation frequently require concomitant administration of drugs, and inhaled drugs in many cases are highly desirable. Inhaled drugs are normally delivered as an aerosol from a nebulizer. Thus, the administration of aerosolized (also termed“atomized”) drugs to patients on a mechanical ventilator is an important medical issue. The issues include maximizing efficient delivery of the drug to the lungs of the patient, which may be expensive. Inefficient drug delivery wastes drug and may cause undesirable exposure of drug to surrounding persons.

[0004] Prior art approaches to administering aerosolized drug to patients typically involve nebulizers. Previous examples of nebulizers include the disclosures W02016/019061 A1 and WO 2015/188179 A1. In some cases, special nebulizers have been designed to mate with specific ventilators. However, studies have shown the efficiency of prior art nebulizers can be excessively variable, resulting in inaccurate or unpredictable drug administration that can cause overdosing or underdosing of drug to the patient. Thus, accurate and predictable dosing is important. [0005] Another issue is the administration of atomized medications with concomitant humidification. Normally, patients on a mechanical ventilator require humidification of the inspired air or other gases. However, the atomization of many drugs with humidification can be a problem. Conventionally, there has been concern about using humidified gases during the nebulization process, and that nebulization would not work properly or be less efficient with humidified gases input into a nebulizer. See Arzu Ari et al.,“Influence of Nebulizer Type, Position, and Bias Flow on Aerosol Drug Delivery in Simulated Pediatric and Adult Lung Models During Mechanical Ventilation,” Respir Care 2010; 55(7): 845- 851 (abstract). Alternatively, placing a humidifier after the nebulizer has raised another set of problems of contamination of the humidifier with drug.

[0006] Another issue is managing the ventilator circuit to minimize interruption to the breathing of the patient. In some cases, it may desirable to remove a nebulizer to refill it or replace it. At the same time, turning off the entire circuit, even momentarily, can be a problem for patients on a mechanical ventilator that require continuous assisted breathing.

[0007] Positive pressure ventilator circuits for assisted breathing are well known, see for example the disclosures in US3739776, US4391271 , and US5277125. However, accurate delivery of atomized drug with a nebulizer to patients with concomitant humidification remains an ongoing challenge in these systems.

[0008] The problem addressed by this invention is that aerosol delivery during mechanical ventilation is often uncontrolled and a function of duty cycle, bias flow, nebulizer position and humidification. This invention discloses a novel system that minimizes these influences with a design that functions independently of ventilator brand and generates aerosol primarily during inspiration (breath enhancement) and minimizes expiratory losses (breath actuation).

SUMMARY OF THE INVENTION

[0009] In one aspect, this invention is based on the unexpected finding that the humidifier in a ventilation circuit with nebulized delivery of aerosolized drug can be placed before the nebulizer if the appropriate nebulizer is used, and by controlling the degree of humidification, which can be accomplished by proper placement of temperature sensors.

[0010] In another aspect, this invention provides a valve so that the inspiratory airflow can be switched between passage through the nebulizer to provide drug to the patient, or to cause the airflow to bypass the nebulizer so no drug is provided to the patient. [0011] In another aspect, this invention can provide uninterrupted regulated airflow to the patient, using a two-way selector valve and a T-fitting, which can isolate the nebulizer from the circuit. The nebulizer can thereby be safely removed for recharging or replacement without affecting the airflow through the circuit.

[0012] In another aspect, this invention provides breath-actuated nebulization, so that drug is only atomized in the nebulizer, and aerosolized drug is only formed, when the patient is actually inhaling. This may be termed the“duty cycle.” When the patient is exhaling or not inhaling, no drug is atomized in the nebulizer.

[0013] In an alternative aspect, this invention provides continuous nebulization, so that drug is atomized continuously in the nebulizer as long as there is drug solution in the nebulizer.

[0014] Thus, in an embodiment, a ventilator circuit apparatus is provided for the administration of an aerosolized medication from a nebulizer through an endotracheal tube to a patient on a medical ventilator. The apparatus may include means (as described herein) to disconnect the nebulizer without interrupting the airflow to the patient.

[0015] In an embodiment, this invention provides an inspiratory tube connected to an endotracheal tube intubated into a patient through a Y-connection and an expiratory tube that is connected from the Y connection to the expiratory input of the ventilator. The inspiratory tube is in fluid communication with a first port of a first T-fitting. A third port of the first T-fitting is connected to the output port of a nebulizer, wherein a ball valve in the connection has an open position allowing fluid communication between the first T-fitting and the nebulizer and a closed position that stops the fluid communication between the first T-fitting and the nebulizer. The second part of the first T-fitting is in fluid communication through a tube to a second T-fitting.

[0016] In an embodiment, this invention provides a ventilator circuit apparatus for the administration of an aerosolized medication from a nebulizer through an endotracheal tube to a patient on a medical ventilator, wherein the medical ventilator provides breathing gases to the patient. In an embodiment, the apparatus uses an endotracheal tube intubated into a patient and connected to the stem of a Y-connection, wherein one branch of the Y-connection is an inspiratory conduit, and the other branch of the Y-connection is an expiratory conduit connected from the Y-connection to the expiratory input of the ventilator. The inspiratory conduit may be in fluid communication with a first port of a T-fitting. A second port of the T-fitting may be connected to the output port of a nebulizer, and a third port of the T-fitting may be in fluid communication through a conduit to a first port of a two-way selector valve. The input port of the nebulizer may be in fluid communication with a second port on the two-way selector valve. A third port of the two-way selector valve may be in fluid communication with the output port of a humidifier, wherein the inspiratory output port of the ventilator is in fluid communication with the input port of the humidifier. In an embodiment the two-way selector valve has a two-position stopcock with a first position causing the breathing gas flow to bypass the nebulizer flow to the inspiratory conduit. The two-position stopcock has a second position in which all breathing gases flow from the humidifier to the input port of the nebulizer, and the nebulizer provides nebulized drug to the patient through the inspiratory limb of the ventilator circuit. Thus, all breathing gases to the patient flow through the nebulizer in this second position.

[0017] Several nebulization modes are possible with the inventive apparatus. In an

embodiment, there is continuous nebulization, meaning that the nebulizer is active as soon as the apparatus is in place and continuously nebulizes drug regardless of the inhalation/exhalation status of the breathing cycle. In an alternative embodiment, breath-activated nebulization is used. In this embodiment, a pressure sensor is interposed between the mechanical ventilator inspiratory output and the two-way selector valve. The pressure sensor can detect an increase in pressure indicative of an inhalation portion of a breathing cycle. During an inhalation event, the pressure sensor activates the nebulizer to cause nebulization to occur during the inhalation portion of the breathing cycle. When the inhalation portion of the breathing cycle stops, the pressure sensor detects a decrease in pressure between the mechanical ventilator and the two- way selector valve, and the pressure sensor causes the nebulizer to stop nebulization.

[0018] In an embodiment, the nebulizer is a jet nebulizer. In this embodiment, breath actuated nebulization can be provided, with a pressure sensor interposed between the mechanical ventilator and the two-way selector valve that detects an increase in pressure indicative of an inhalation portion of a breathing cycle. During the inhalation portion of the breathing cycle the pressure sensor signals a solenoid to activates pressurized air to the jet nebulizer to cause nebulization to occur in the nebulizer. When the inhalation portion of the breathing cycle stops, the pressure sensor detects a decrease in pressure between the mechanical ventilator and the two-way selector valve, and the pressure sensor signals the solenoid to switch off the pressurized air to the nebulizer to stop nebulization. Thus, the default mode in this embodiment is no nebulization, even though all breathing gasses to the patient are flowing through the nebulizer. [0019] In an embodiment, the nebulizer on the ventilator circuit apparatus includes is a breath- enhanced nebulizer. The nebulization with a breath- enhanced nebulizer may be continuous or breath actuated as described herein.

[0020] In an embodiment, the nebulizer includes a port allowing additional drug to be added to the nebulizer while it is in use. The addition of drug to the nebulizer may be via an infusion drip or syringe pump.

[0021] In an embodiment, the nebulizer is removable from the ventilator circuit apparatus without interrupting the air flow to the patient. In this embodiment, a ball valve is interposed between the T-fitting and the output port of the nebulizer. The ball valve has an on and off position. In the“off” position, the ball valve blocks fluid communication between the nebulizer and the inspiratory conduit. By switching the ball valve to the“off” position and switching the two-way selector valve to bypass the nebulizer, the nebulizer is completely isolated from the ventilation circuit. When so isolated, the nebulizer is removable without interrupting breathing gas flow to the patient.

DESCRIPTION OF THE DRAWINGS

[0022] Fig. 1A is a schematic of an embodiment of the inventive ventilator circuit apparatus where breathing gases a channeled through the nebulizer.

[0023] Fig. 1 B is a breakout of the apparatus of Fig. 1 A but where the breathing bases bypass the nebulizer.

[0024] Fig. 2 is a schematic of an alternative configuration of the ventilator circuit apparatus, showing breathing gas flow through the nebulizer and including the ball valve.

[0025] Fig. 3 is a schematic of the embodiment of Fig. 2, showing breathing gas flow through the nebulizer.

[0026] Fig. 4 is a schematic of the embodiment of Fig. 2, showing the breathing gas flow bypassing the nebulizer.

[0027] Fig. 5 is a schematic of the embodiment of Fig. 2, showing the breathing gas flow bypassing the nebulizer and the ball valve on the T-fitting closed, so the nebulizer can be removed without interrupting breathing gas flow to the patient.

[0028] Fig. 6 is an alternative embodiment of the of the ventilator circuit apparatus, with a port for addition of drug to the nebulizer. [0029] Fig. 7 is a plot of aerosol Delivery (IM) for conventional jet nebulizer (“Hudson RCI®”). This data shows fill volume and humidity, with humidity reducing delivery as measured by inhaled mass.

[0030] Fig. 8 is a plot of aerosol Delivery (IM) for mesh nebulizer (Aerogen®). This data shows IM is affected by factors other than fill volume and humidity and delivery cannot be predicted from any defined variable.

[0031] Fig. 9 is a plot of aerosol Delivery (IM) for a breath-enhanced nebulizer (“i-VENT”) with continuous nebulization. This data shows IM delivery is significantly better controlled than the Hudson or Aerogen devices, and is unaffected by fill volume or humidity.

[0032] Fig. 10 is a plot showing infusion pump data for continuous humidified nebulization comparing the i-VENT breath-enhanced nebulizer with the Aerogen mesh nebulizer.

[0033] Fig. 11 shows inhaled mass as a percentage of nebulizer charge vs. ventilator mode and inspiratory time (T,) on the left. Pressure support modes are on the right. Inhaled mass [IM] as % of nebulizer charge vs ventilator mode, inspiratory time [G] left; pressure support modes right: Nebulizer flow 3.5 LPM. VC-CMV ¼ volume control-continuous mandatory ventilation, PC-CMV ¼ pressure control- continuous mandatory ventilation; CRAP + PS = continuous positive airway pressure plus pressure support; PRVC IMV + PS = pressure-regulated volume control with SIMV + pressure support; VC-!MV + PS = volume control-intermittent mandatory ventilation plus pressure support (VC-synchronized intermittent mandatory ventilation = PS); APRV = airway pressure release ventilation (or BiVent).

DETAILED DESCRIPTION

[0034] In an embodiment according to Figs. 1A and 1 B, this invention provides a ventilator circuit apparatus 100 for the administration of an aerosolized medication from a nebulizer 200 through an endotracheal tube 130 to a patient 108 on a medical ventilator 102, wherein the medical ventilator provides breathing gases to the patient. Typically, breathing gases are air, oxygen enriched air, or pure oxygen.

[0035] In an embodiment, the apparatus employs an endotracheal tube 130 intubated into a patient 108 and connected to the stem of a Y-connection 115, wherein one branch of the Y- connection is an inspiratory conduit 110, and the other branch of the Y-connection is an expiratory conduit 120 connected from the Y-connection to the expiratory input 106 of the ventilator 102. Also shown in the drawing is filter 122 on the expiratory input port of the ventilator, that may be intended to trap bacteria, viruses, or drugs from the patient before they enter the ventilator. Also shown is mass filter 134 on the endotracheal tube used in experimental studies to determine the amount of drug reaching the lungs of the patient. The patient is illustrated as a synthetic lung machine for experimental studies, but in clinical practice the endotracheal tube 130 is inserted into the lungs of a patient in respiratory distress. Also shown is closed system suction device 132.

[0036] In an embodiment, the inspiratory conduit 110 of the ventilator circuit apparatus may be in fluid communication with a first port 141 of a T-fitting 140. A second port 142 of the T-fitting may be connected to the output port 201 of a nebulizer, and a third port 143 of the T-fitting may be in fluid communication through a conduit 116 to a first port 151 of a two-way selector valve 150. The input port 202 of the nebulizer may be in fluid communication with a second port 152 on the two-way selector valve. A third port 153 of the two-way selector valve may be in fluid communication with the output port 302 of a humidifier 300, wherein the inspiratory output port 104 of the ventilator is in fluid communication with the input port 304 of the humidifier. As used herein, the term“fluid communication” means that a gas or liquid can pass freely between the two things that are in communication.

[0037] In an embodiment the two-way selector valve has a two-position stopcock 155 with a first position causing the breathing gas flow to bypass the nebulizer 200 and flow to the inspiratory conduit 110 (Fig. 1 B). The two-position stopcock has a second position (Fig. 1A) in which all breathing gases flow from the humidifier to the input port 202 of the nebulizer, and the nebulizer provides nebulized drug to the patient through the inspiratory limb 110 of the ventilator circuit. Thus, all breathing gases to the patient flow through the nebulizer in this second position. In an embodiment, all breathing gases in this circuit therefore flow through the nebulizer or bypass the nebulizer. There is no mixing of nebulized and non-nebulized breathing gases.

[0038] The arrangement and effect of the modes of the two-position stopcock are also illustrated in Figs. 3 and 4. In Fig. 3, the breathing gases from the ventilator and humidifier are all channeled (410) through the nebulizer. In Fig. 4, the two-way selector is changed to the first position and the breathing gases bypass the nebulizer (420). Note it is not necessary to isolate the output port 201 of the nebulizer from the inspiratory conduit in the nebulizer bypass mode as shown in Fig. 4. Also shown in Fig. 3 and 4 is the air flow 400 through the nebulizer.

[0039] Several types of nebulizer devices are known in the art, including jet nebulizers, vibrating mesh nebulizers, and ultrasonic nebulizers. In the embodiment in Figs. 1-6, a jet nebulizer is shown. An embodiment of this type of nebulizer is disclosed in WO 2018/045263 A1 , published 8 March 2018. This nebulizer is called a“mini-NEB™” nebulizer. This type of nebulizer requires a pressurized air supply (Fig. 1A, 220) normally at 50 psi. This air supply via tube 222 drives a Venturi in the nebulizer that causes the drug to be aerosolized. The aerosolization (nebulization) of the drug requires this air supply. If the air supply is stopped, the drug in the nebulizer is not aerosolized.

[0040] In various embodiments, several nebulization modes are possible with the inventive apparatus. In an embodiment, there is continuous nebulization, meaning that the nebulizer is active as soon as the apparatus is in place and continuously nebulizes drug regardless of the inhalation/exhalation status of the breathing cycle, i.e., not cycling on and off with the duty cycle of the patient’s breathing. In some circumstances, and for some drugs, this is a desirable mode. In an alternative embodiment, breath-activated nebulization is used. In an embodiment of breath enhancement, a pressure sensor 212 is interposed between the mechanical ventilator inspiratory output and the two-way selector valve 150. The pressure sensor can detect an increase in pressure indicative of an inhalation portion of a breathing cycle. During an inhalation event, the pressure sensor activates the nebulizer to cause nebulization to occur during the inhalation portion of the breathing cycle. When the inhalation portion of the breathing cycle stops, the pressure sensor detects a decrease in pressure between the mechanical ventilator and the two-way selector valve, and the pressure sensor causes the nebulizer to stop nebulization.

[0041] In an embodiment, breath actuated nebulization is provided with a jet nebulizer. In an embodiment, a pressure sensor 212 is interposed between the mechanical ventilator inspiratory output 104 and the two-way selector valve 150 that detects an increase in the pressure of the breathing gas flow from the ventilator indicative of an inhalation portion of a breathing cycle. During the inhalation portion of the breathing cycle the pressure sensor signals a solenoid 210 via cable 214 to activate pressurized air 220 to flow to the jet nebulizer 200 via tube 222 to cause nebulization to occur in the nebulizer. When the inhalation portion of the breathing cycle stops, the pressure sensor detects a decrease in pressure between the mechanical ventilator and the two-way selector valve, and the pressure sensor signals the solenoid 210 to switch off the pressurized air to the nebulizer to stop nebulization. Thus, the default mode in this embodiment is no nebulization, even though all breathing gasses to the patient are flowing through the nebulizer. In another embodiment, a breath actuated valve may be part of the nebulizer that deactivates the nebulization during portions of the breathing cycle except during an inhalation. [0042] In an embodiment, the nebulizer on the ventilator circuit apparatus includes is a breath- enhanced nebulizer. An example of a breath-enhanced nebulizer is disclosed in

WO 2019/236896 A1 , published 12 December 2019. In this type of nebulizer, called an i- VENT™ nebulizer, the Venturi effect is amplified by the internal configuration of the nebulizer to increase the rate of nebulization of drug. The nebulization with a breath-enhanced nebulizer may be continuous or breath actuated as described herein.

[0043] In an embodiment, the nebulizer includes a port 206 allowing additional drug to be added to the nebulizer 200 while it is in use (Fig. 6). This type of port is disclosed in

WO 2019/236896 A1 , published 12 December 2019. The addition of drug to the nebulizer may be via an infusion drip or syringe pump.

[0044] Figs. 2-5 show an alternative embodiment of the ventilator circuit apparatus having a slightly different configuration of the two-way selector valve, nebulizer, and T-fitting. Also shown in Figs. 2-5 is ball valve 144 used in the embodiment where the nebulizer is removable without interrupting breathing gas flow to the patient. Ball valve 144 however, is optional.

[0045] In an embodiment (Fig. 5), the nebulizer 200 is removable from the ventilator circuit apparatus without interrupting the air flow to the patient. This can be important. Patients on a ventilator may be in respiratory distress and unable to breathe on their own, so interrupting the airflow to the patient, even momentarily, is undesirable. In this embodiment, a ball valve is interposed between the T-fitting and the output port 201 of the nebulizer. The ball valve has an on and off position. In the“off” position, the ball valve blocks fluid communication between the output port of the nebulizer and the inspiratory conduit. By switching the ball valve to the“off” position and switching the two-way selector valve to bypass the nebulizer, the nebulizer is completely isolated from the ventilation circuit. When so isolated, the nebulizer is removable without interrupting breathing gas flow to the patient. This is illustrated in Fig. 5 with the nebulizer shown as 204 in dashed lines, and two-way selector valve 150 and ball valve 144 configured to isolate the nebulizer from the ventilator circuit for removal.

[0046] The embodiment in Fig. 1 includes a humidifier 300 to humidify the breathing gases. In this embodiment, the humidifier is in front of the nebulizer 200. That is, the breathing gases flow from the mechanical ventilator to the humidifier 300 via conduit 118 and then to the nebulizer via conduit 119, if the nebulizer is in use. Thus, the nebulization may be termed“wet nebulization,” indicated that humidified gases are input into the nebulizer at the nebulizer input port 202. This is believed to have certain advantages in the administration of nebulized drugs to an intubated patient. Humidified breathing gases are necessary for the patient. Attempts to put the nebulizer after the humidifier can foul the water in the humidifier and gives less control over the degree of humidification.

[0047] The inventor found that with proper humidity control at the input port to the nebulizer 202, nebulization works very well, in contrast to conventional thinking that the nebulization must be dry. The instant invention found that with proper humidity control as described herein, there is no significant difference in nebulization rate or the rate of drug, and the placement of the nebulizer on the west side of the humidifier avoids complications in conventional set-ups with nebulizer on the dry side of the nebulizer. When the nebulizer is on the dry side of the humidifier, aerosolized drug enters the humidifier. The inventor found that significant, yet variable amounts of drug would be trapped in the humidifier. In some experiments, up to 17% of the nebulized drug mass was absorbed into the nebulizer water. This contaminates the humidifier, and unpredictably reduces the drug dosage delivered to the patient.

[0048] The degree of humidification in the embodiments of Figs. 1-6 is controlled by at least two temperature sensors, shown as 320 on the inspiratory line at the Y-connector 115, and 310 located between the output port 302 of the humidifier and the two-say selector valve 150. In addition, typically the inspiratory limb 110 is embedded with heating elements that can adjust the temperature of the gases moving through tube 110. Cable 322 transmits the temperature data to the humidifier.

[0049] The objective of the humidification control in a ventilator apparatus such as shown in Fig. 1 is to provide breathing gases and optionally an aerosolized drug at 37°C and 100% humidity at the Y-connection 115. Ultimately, with a humidifier, this degree of humification is a function of the water temperature in a water bath in the humidifier. Several inputs and outputs can be employed to control the temperature and humidification. The two temperature probes 310 and 320 can work in conjunction with heating coils embedded in the inspiratory tube 110 that are computer controlled to provide inspiratory breathing gases at the Y connection at the correct temperature and humidity.

[0050] The inventor found that the temperature probe 310 at the output of the humidifier may be important to the success of this apparatus. This helps control the amount of humidity going into the nebulizer, and prevents over-humidification in this region of the circuit, which can cause pooling of water and difficulties in the nebulization from water droplets forming inside the inspiratory line of the ventilator between the nebulizer and the Y connector. [0051] Figs. 7-11 are data plots showing the performance of the inventive apparatus, with wet nebulization, coupled to an“i-VENT” BEN/BAN compared to some alternative nebulizer technologies. Fig. 7 is a plot of aerosol delivery as measured at the inhaled mass (IM) filter 134 or equivalent, for a conventional jet nebulizer (“Hudson RCI®”). This data was generated with a setup similar to Figs. 1 or 2, except that the Hudson jet nebulizer was used instead of an i- VENT™ nebulizer. This data shows fill volume and humidity, with humidity (i.e. , the Fig. 1 embodiment) reducing delivery of drug as measured by inhaled mass. Fill volume of the nebulizer is a factor in the efficiency of aerosolization of the nebulizer. Ti is the inhalation time, which in this apparatus can be set by adjustments to the artificial lungs 108. It is apparent from the data in Fig. 7 that the efficiency of the nebulization, especially at the lower fill volume, is lower when humidified air was used in the nebulizer.

[0052] Fig. 8 is a plot of aerosol Delivery (IM) for a mesh nebulizer (Aerogen®). This data shows IM is affected by factors other than fill volume and humidity and delivery cannot be predicted from any defined variable. Note particularly the data point at 0.7 Ti and 6 ml_ volume without humidification, which is zero. A problem the inventor has noted with the Aerogen mesh nebulizers is a certain number of total and partial failures to deliver drug. Presumably this is a surface tension effect, in which the drug solution in the nebulizer does not reach the membrane so nebulization does not occur. This is a potential disadvantage to this type of nebulizer in the inventive apparatus.

[0053] Fig. 9 is a plot of aerosol Delivery (IM) for the i-VENT™ breath-enhanced nebulizer. This data shows IM delivery is significantly better controlled than the Hudson or Aerogen devices, and is unaffected by fill volume or humidity. There are consistent data trends for all four modes studied with the i-VENT™.

[0054] Fig. 10 is a plot showing infusion pump data for humidified nebulization comparing the i- VENT breath-enhanced nebulizer with the Aerogen mesh nebulizer. The data for the two methods is comparable except that the Aerogen device exhibits frequent failures at the higher infusion rates.

[0055] Fig. 11 shows data for various ventilation machines and the i-Vent™ breath enhanced nebulizer with humidification, i.e., wet nebulization as in Fig. 1 , vs. dry nebulization. The nebulizer flow is 3.5 LPM. Drug is measured from an inhaled mass filter (134) on the inspiratory line leading a simulated patient (i.e., 108). In Fig. 12, the data on left is for controlled ventilation modes, in which the machine controls all the breathing of the patient. The essential parameter that can be varied with any ventilator is the inhalation time. By controlling the inhalation time (Ti), various ventilator machines can be directly compared. The left data in Fig. 12 compares data from three ventilator machines. The outline symbols are for wet nebulization, and the solid symbols are for dry nebulization. This data shows there is no systematic effect on IM (i.e. , dose of drug delivered to the patient) for any ventilator setting or mode of ventilation. Effects of humidification are reduced and much less than conventional nebulization. There are statistical differences of IM with and without humidification, but these are clinically not relevant, as the magnitude of the difference is less than conventional nebulization (eg the Hudson data in Fig.

8). This data shows that the IM with humidification is equivalent to, or better than, prior art dry nebulization.

[0056] The four modes on the right side of Fig. 11 are various pressure support ventilation modes, where the patient participates in the breathing. No clinically relevant effects are seen for any mode of ventilation with or without humidification. As with the left side of Fig. 11 , this data shows no systematic effect on IM (i.e., dose of drug delivered to the patient) for any ventilator setting or mode of ventilation. Effects of humidification are reduced and much less than conventional nebulization. There are statistical differences of IM with and without humidification, but these are clinically not relevant, as the magnitude of the difference is less than conventional nebulization.

[0057] This data in Fig. 11 supports the contention that wet nebulization, as in this invention, has superior drug delivery than prior art wet nebulization set-ups where drug delivery was reported to be reduced by as much as 60%..

Legend for drawings

Claims

1. A ventilator circuit apparatus for the administration of an aerosolized medication from a nebulizer through an endotracheal tube to a patient on a medical ventilator, wherein the medical ventilator provides breathing gases to the patient, comprising:

a. an endotracheal tube intubated into a patient and connected to the stem of a Y- connection, wherein one branch of the Y-connection is an inspiratory conduit, and the other branch of the Y-connection is an expiratory conduit connected from the Y-connection to the expiratory input of the ventilator;

b. wherein the inspiratory conduit is in fluid communication with a first port of a T- fitting;

c. wherein a second port of the T-fitting is connected to the output port of a

nebulizer;

d. wherein a third port of the T-fitting is in fluid communication through a conduit to a first port of a two-way selector valve;

e. wherein the input port of the nebulizer is in fluid communication with a second port on the two-way selector valve;

f. wherein a third port of the two-way selector valve is in fluid communication with the output port of a humidifier;

g. wherein the inspiratory output port of the ventilator is in fluid communication with the input port of the humidifier;

h. wherein the two-way selector valve has a two-position stopcock with a first

position bypassing breathing gas flow to the nebulizer and providing fluid communication between the output port of the humidifier and the inspiratory conduit, and the two-position stopcock has a second position in which all breathing gases flow from the humidifier to the input port of the nebulizer, and the nebulizer provides nebulized drug to the patient through the inspiratory limb of the ventilator circuit.

2. The apparatus of claim 1 , wherein there is continuous nebulization.

3. The ventilator circuit apparatus of claim 1 , further comprising a pressure sensor between the mechanical ventilator and the two-way selector valve that detects an increase in pressure indicative of an inhalation portion of a breathing cycle, and wherein the pressure sensor activates the nebulizer to cause nebulization to occur during the inhalation portion of the breathing cycle, and wherein when the inhalation portion of the breathing cycle stops, the pressure sensor detects a decrease in pressure between the mechanical ventilator and the two-way selector valve, and the pressure sensor causes the nebulizer to stop nebulization.

4. The apparatus of claim 1 , wherein the nebulizer is a jet nebulizer.

5. The ventilator circuit apparatus of claim 4, further comprising a pressure sensor between the mechanical ventilator and the two-way selector valve that detects an increase in pressure indicative of an inhalation portion of a breathing cycle, and wherein the pressure sensor signals a solenoid to activate pressurized air to the jet nebulizer to cause nebulization to occur in the nebulizer, and wherein when the inhalation portion of the breathing cycle stops, the pressure sensor detects a decrease in pressure between the mechanical ventilator and the two-way selector valve, and the pressure sensor causes the solenoid to switch off the pressurized air to the nebulizer to stop nebulization.

6. The apparatus of claim 1 , wherein the nebulizer is a breath enhanced nebulizer.

7. The ventilator circuit apparatus of claim 1 , further comprising a ball valve interposed between the T-fitting and the nebulizer, and wherein the nebulizer is isolated from the circuit by switching the two-way selector valve to bypass the nebulizer and the ball valve to a position blocking fluid communication between the nebulizer and the inspiratory conduit, and wherein the nebulizer is removable without interrupting breathing gas flow to the patient.

8. The apparatus of claim 1 , wherein the nebulizer includes a port allowing additional drug to be added to the nebulizer while it is in use.

9. The apparatus of claim 8, wherein the addition of drug to the nebulizer is via an infusion drip or syringe pump.