Patent Application
20210236750
This invention pertains to the administration of nebulized drugs to patients connected to a mechanical ventilator breathing circuit.
The administration of nebulized drugs to patients on a mechanical ventilator is an important medical need. Challenges in the administration of nebulized drugs to patients on a mechanical ventilator include maximizing efficient delivery of the drug to the lungs of the patient and provision of properly humidified breathing gases. Inefficient drug delivery wastes drug product, which may be expensive, may cause unpredictable dosing to patients (too much or too little drug), and may cause undesirable exposure of drug to surrounding persons. As used herein, the term “nebulized” is also referred to as “atomized” or “aerosolized,” and all three terms are interchangeable. The term “drug” as used herein is interchangeable with “pharmaceutical composition.”
Prior art approaches to administering nebulized drugs to patients on a ventilator typically involve nebulizers incorporated into a breathing circuit. Among the challenges of the administration of nebulized drugs in a breathing circuit are maintaining appropriate humidification and minimizing the variability in drug delivery to the patient.
Normally, patients on a mechanical ventilator require humidification of the inspired air or other gases. However, the nebulization of many drugs with humidification may be a problem. The humidification can interfere with the formation and transfer of appropriately sized droplets of an atomized drug composition. Thus, in many cases, it is desirable to nebulize a drug composition without humidification.
Another issue is managing the ventilator circuit to minimize interruption to the breathing of the patient. It is typically desirable to remove a nebulizer to refill it or clean it. At the same time, turning off the entire circuit, even momentarily, can be a problem for patients on a mechanical ventilator.
Nebulized aerosol delivery during mechanical ventilation results in profound unregulated aerosol losses, which are a strong function of duty cycle or the inhalation-exhalation (I/E) ratio, bias flow, and humidification. Previous studies have suggested that humidification during nebulization may reduce drug output (T. G. O'Riordan, G. C. Smaldone, et al., “Nebulizer Function during Mechanical Ventilation,” Am Rev Respir Dis. 1992 May; 145(5):1117-22, https://doi.org/10.1164/ajrccm/145.5.1117, PubMed 1586056; P. Diot and G. C. Smaldone et al., “Albuterol Delivery in a Model of Mechanical Ventilation,” Am J Respir Crit Care Med 1995, 152, 1391-1394, doi: 10.1164/ajrccm.152.4.7551401; D. D. Miller, G. C. Smaldone et al., “Aerosol Delivery and Modern Mechanical Ventilation, In Vitro/In Vivo Evaluation,” Am J Respir Crit Care Med, 2003, 168, 1205-1209, doi: 10.1164/rccm.200210-1167OC (see table 1)).
Ventilation circuits have previously been described in, e.g., US 2014/0238397 A1, published Aug. 24, 2014, and US 2015/0108670 A1, published Apr. 23, 2015.
The present invention describes a novel ventilator circuit that minimizes the influences of duty cycle or the inhalation-exhalation (I/E) ratio, bias flow, and humidification by utilizing a design that results in aerosol generation primarily during inspiration (breath enhancement) and minimizes expiratory losses (breath-actuation). The circuit facilitates control of supplemental humidification and functions independently of the brand of the ventilator.
Also, in view of the references cited above (O'Riordan, Diot, and Miller), suggesting that humidification during nebulization on breathing circuits with mechanical ventilation may reduce drug output, the instant invention is designed to provide the benefits of dry nebulization, humidification as required, and isolation of the nebulizer for efficient removal without interrupting the breathing.
In a first aspect, a ventilator circuit apparatus is provided for the administration of nebulized drugs through an endotracheal tube to a patient on a mechanical ventilator that controls breathing gases to the patient. The apparatus has a breathing circuit with an inspiratory limb and exhalation limb connected to the ventilator; a nebulizer on the inspiratory limb interposed between a T-fitting and a three-way valve such that the nebulizer can be removed from the inspiratory limb without interrupting the flow of breathing gases to the patient; and a humidifier or heat and moisture exchanger (HME) on the inspiratory limb interposed between the nebulizer and the endotracheal tube. In an embodiment, all breathing gases to the patient flow through the ventilator circuit. In an embodiment, the nebulizer is a jet-nebulizer. In an embodiment, the nebulizer is breath-actuated, further comprising a pressure sensor interposed between the nebulizer and the ventilator, wherein the pressure sensor controls a pressurized air supply to the nebulizer required for nebulization to occur, such that nebulization only occurs during a pressure increase on the inspiratory limb caused by an increase in air pressure from the ventilator to force an inhalation by the patient. In an embodiment, the nebulizer is breath-enhanced.
In another aspect, a ventilator circuit apparatus is provided for the administration of nebulized drugs through an endotracheal tube to a patient on a mechanical ventilator that provides breathing gases for inhalation by the patient. In an embodiment, the apparatus has an inspiratory tube connected to an endotracheal tube intubated into a patient; a ventilator circuit comprising a T-fitting with three connections, wherein a first connection to the T-fitting is connected to the inspiratory tube, wherein a second connection of the T-fitting is connected to the output port of a humidifier, and wherein a third connection of the T-fitting is connected to the output port of a nebulizer; wherein the input port of the nebulizer is connected to a three-way valve, and wherein a second connection of the three-way valve is connected to the input port of the humidifier, and wherein a third connection of the three-way valve is connected to an inspiratory output of the mechanical ventilator; wherein in a first position of the three-way valve, the circuit is open that bypasses the nebulizer and directly connects the inspiratory output of the mechanical ventilator to the humidifier, and in a second position of the 3-way valve, the inspiratory output of the mechanical ventilator bypasses the humidifier and is directed to the nebulizer; wherein in the second position of the three-way valve, a drug solution in the nebulizer is nebulized to deliver nebulized drug to the inspiratory tube wherein the nebulized drug is inhaled by the patient; and wherein in the first position of the three-way valve, humidified breathing gases are delivered to the inspiratory tube. In an embodiment, a temperature sensor is provided on in the inspiratory tube that controls the amount of water vapor produced by the humidifier. In an embodiment, one or two connections to the T-fitting have a spring-loaded self-sealing fitting, permitting a tube inserted in the connection to be pulled out, whereupon the connection to self-seals.
In another aspect, a ventilator circuit apparatus is provided for the administration of nebulized drugs through an endotracheal tube to a patient on a mechanical ventilator that provides breathing gases for inhalation by the patient. In this embodiment, the apparatus has an inspiratory tube in fluid communication with an endotracheal tube intubated into a patient; a ventilator circuit comprising a T-fitting with three connections, wherein a first connection to the T-fitting is connected to the inspiratory tube, wherein a second connection of the T-fitting is connected to a three-way valve, and wherein a third connection of the T-fitting is connected to the output port of a nebulizer; wherein the input port of the nebulizer is connected to the three-way valve, and wherein a third connection of the three-way valve is connected to an inspiratory output of the mechanical ventilator; wherein in a first position of the three-way valve, the circuit is open that bypasses the nebulizer and directly connects the inspiratory output of the mechanical ventilator to the inspiratory tube, and in a second position of the 3-way valve, the inspiratory output of the mechanical ventilator is directed to the nebulizer; and wherein in the second position of the three-way valve, a drug solution in the nebulizer is nebulized to deliver nebulized drug to the inspiratory tube wherein the nebulized drug is inhaled by the patient. In an embodiment, a heat and moisture exchanger (HME) with a bypass mode is on the inspiratory tube such that when the three-way valve is in the first position, the HME delivers humidified breathing gases to the patient, and when the three-way valve is in the second position, the HME is switched to bypass mode.
In another aspect, the ventilator circuit apparatus for the administration of nebulized drugs through an endotracheal tube to a patient on a mechanical ventilator that provides breathing gases for inhalation by the patient. In this embodiment, the apparatus has an inspiratory tube connected to an endotracheal tube intubated into a patient; a ventilator circuit comprising a T-fitting with three connections, wherein a first connection to the T-fitting is connected to the inspiratory tube, wherein a second connection of the T-fitting is connected by a tube to a first connection on a three-way valve, and wherein a third connection of the T-fitting is connected to the output port of a nebulizer; wherein the input port of the nebulizer is connected to a second connection of the three-way valve, and wherein a third connection of the three-way valve is connected to an inspiratory output of the mechanical ventilator; wherein in a first position of the three-way valve, the circuit is open that bypasses the nebulizer and directly connects the inspiratory output of the mechanical ventilator to the inspiratory tube, and in a second position of the 3-way valve, the inspiratory output of the mechanical ventilator is directed to the nebulizer; and wherein in the second position of the three-way valve, a drug solution in the nebulizer is nebulized to deliver nebulized drug to the inspiratory tube wherein the nebulized drug is inhaled by the patient. In an embodiment, a ball-valve is interposed between the T-fitting and the nebulizer. In an embodiment, a ball-valve is interposed between the T-fitting and the nebulizer, and when the three-way valve is in position one and the ball valve is closed, the nebulizer can be removed from the ventilator circuit without interrupting the flow of breathing gases to the patient. In an embodiment, a temperature sensor is provided on in the inspiratory tube that controls the amount of water vapor produced by the humidifier. In an embodiment, the apparatus has an HME.
In another aspect, a method is provided of administering a nebulized drug with any of the apparatus embodiments of this invention.
In embodiments, the present invention uses breath-enhanced nebulizers. In an embodiment, the nebulization may be breath-activated. Prior art breath-enhanced nebulizers have only been used with spontaneously breathing patients. Using a breath-enhanced nebulizer with a mechanical ventilator and a breathing circuit allows further enhances the patient's berating and facilitates the desired drug intake.
The present inventors have found that breath-enhanced nebulizers, such as those disclosed in this invention, can significantly increase the fraction of drug that is inhaled by the patient and delivered to the lungs (as measured by an inhaled mass (IM) filter in a test apparatus). Moreover, the BEN can significantly shorten the time required to nebulize a particular dose of medication, which can be a significant advantage to the care facility.
Disclosed herein is a breathing circuit for the administration of nebulized drugs to a patient breathing with the aid of a mechanical ventilator and a breathing circuit. In an embodiment, part of the circuit is a nebulizer, which nebulizes a drug solution for inhalation of the drug by a patient. In an embodiment, the nebulizer is a jet nebulizer that nebulizes drug solutions by shear forces from a compressed air supply to the nebulizer jet. In an embodiment, the nebulizer is another type of nebulizer, for example, a vibrating mesh nebulizer or an ultrasonic nebulizer.
In operation, a three-way valve may be included that has two operating positions. A second position directs all ventilator flow to the nebulizer resulting in an aerosol generation, which may be limited to nebulization during the inhalation portion of a breathing cycle only. In a first operating position of the three-way valve, the breathing gases from the ventilator bypass the ventilator and pass instead either directly to the inspiratory limb of the breathing circuit, or pass to the inspiratory limb through a humidifier. In an embodiment, special connections in the ventilator circuit bypass the nebulizer and allow for nebulizer removal for servicing without breaking the air flow in the circuit or interrupting breathing to the patient.
In an embodiment, the nebulizer used in this invention is a jet-nebulizer and generates aerosol by nebulization only when a nebulizer air flow is provided. An exemplary nebulizer is that disclosed in co-pending patent application [ ], filed [ ], and based on U.S. Provisional Patent Application No. 62/681,654 filed Jun. 6, 2018. As disclosed therein, breath-enhanced and breath-actuated nebulizers are provided.
Breath-enhanced nebulizers have an internal configuration that enhances, or amplifies, the rate of nebulization compared to prior art jet nebulizers. Embodiments of breath-enhanced nebulizers are disclosed in co-pending patent application [ ], based on U.S. Provisional Patent Application No. 62/681,654. Other types of nebulizers may also be useful in this invention, including other jet nebulizer designs, vibrating mesh, and ultrasonic nebulizers that can be used in a breathing circuit controlled by a mechanical ventilator.
In an embodiment, the nebulization is breath actuated. With a breath actuated nebulizer, compressed air is only provided to the nebulizer while the patient is inhaling. This is controlled with a pressure sensor that toggles the nebulizer air flow on or off as required. The inhalation portion of a breathing cycle is also termed the “duty cycle,” the fraction of time of an overall inhalation/exhalation cycle when the patient is actually inhaling. In an embodiment, breath-actuation relies on a pressure sensor that can detect when a patient is inhaling, as opposed to exhaling or neither inhaling nor exhaling, and the sensor can activate a solenoid that provides compressed air to the nebulizer. In an embodiment, the pressure sensor is placed on a tube in fluid communication with the inspiratory outlet of the mechanical ventilator. When the ventilator causes the patient to inhale by increasing the air pressure at the inspiratory outlet, the pressure sensor detects this increase and switches on a nebulizer air flow to the nebulizer, which drives the jet nebulizer and causes nebulization to occur. Other means of toggling nebulization are possible with other types of nebulizers. For example, with an electrically driven vibrating mesh or ultrasonic nebulizer, a pressure sensor can control the power supply that drives the nebulization.
In an aspect of this invention, the nebulized drug is provided by the inventive breathing circuits in such a way the humidification is not used during nebulization. This may be a desirable feature based on previous studies (O'Riordan, Diot, and Miller, cited above) suggesting much lower nebulizer efficiency if a humidifier is placed before the nebulizer, so that humidified air or other breathing gases enter the nebulizer. As used herein, the term “breathing gases” means either ordinary air or another breathing gas mixture indicated for use in mechanical ventilation, such as oxygen enriched air.
In an embodiment of this invention, the entire mass of breathing gases in the inspiratory tract passes through the nebulizer when the nebulizer is active.
In an embodiment of this invention as shown in
In clinical practice, an endotracheal tube would be used by a patient on a ventilator circuit such as disclosed in
In an embodiment, nebulizer 101, as discussed herein, produces an aerosol (when active) that is shunted through a T-fitting 106 to the inspiratory line 107 and the endotracheal tube 108 positioned downstream of the inspiratory line 107 where it is inhaled by the patient 110.
In an embodiment, the nebulizer 101 is breath-actuated, further comprising a pressure sensor 114 interposed between the nebulizer 101 and the ventilator 102 wherein the pressure sensor controls a pressurized air supply 117 to the nebulizer required for nebulization to occur, such that nebulization only occurs during a pressure increase on the inspiratory limb caused by an increase in air pressure from the ventilator to force an inhalation by the patient. In an embodiment, pressure sensor 114 is in electronic communication with solenoid valve 116 via electrical connection 115 that toggles the supply of compressed air 117 on and off. When the pressure at 114 increases, signaling an inhalation phase of the breathing cycle, pressure sensor 114 activates solenoid 116 to toggle on, supplying compressed air 117 to nebulizer 101 via nebulizer air supply line 118, which causes nebulization to start. When the ventilator reduces the air pressure at port 103, pressure sensor 114 detects that the inhalation phase has stopped, and solenoid valve 116 toggles off stopping the compressed air to nebulizer 101, which stops nebulization. Nebulization will not take place with jet nebulizer 101 unless air supply line 118 is active.
In an embodiment where a jet nebulizer is used, nebulizer compressed air 117 typically at 50 psig is used to drive the jet. Nebulizer flows of 2 L/min in the continuous mode and 3.5 L/min during breath actuation (typical rates; other flow rates are possible) are used with jet nebulizers.
In an embodiment, the nebulizer is breath-enhanced, which is discussed above.
In an embodiment, humidifier 121 supplies properly humidified breathing gases to the patient, ideally at 100% humidity and 37° C. at Y-connector 127. Regulation of the amount of humidity in the circuit is important. With too much humidity, water will tend to condense inside the circuit which is undesirable. With too little humidity, the patient will be uncomfortable and secretions can increase. The humidity may be controlled, at least in part, by temperature sensor 128 in Y-connector 127, that is linked to the humidifier by wire 129. In addition, inspiratory limb 107 may include internal heating elements to heat the breathing gases to an appropriate temperature.
In an alternative embodiment, instead of a humidifier, a heat and moisture exchanger (HME) 125 may be employed. This is illustrated in
In the operation of the three-way valve 105, during the inhalation phase of a breathing cycle, breathing gases from the mechanical ventilator inspiratory output port 103 are directed to the three-way valve with a stopcock 105. As shown in
In an embodiment, a closed system suction device 128, may be attached to the breathing tube 108 to allow the removal of secretions from the upper respiratory tract without having to open the ventilation circuit.
For studies of the performance of the inventive configuration and/or various nebulizers, an inhaled mass filter (IM filter) 111 and a Cascade impactor 112 attached to the breathing tube 108 can be used to measure the dose of drug delivered to the patient (
In an embodiment, the T-fitting has one or two spring-loaded self-sealing fittings. Such fittings include an internal mechanism opening the airway when a tube is inserted into the fitting. When the tube is removed, a valve closes from the force of a spring, sealing the opening. In an embodiment, a spring-loaded self-sealing fitting 132 is positioned at the T-fitting connection attached to the nebulizer. In an embodiment, another spring-loaded self-sealing fitting 124 is used at the T-fitting connection attached to the humidifier. With these self-sealing fittings, the attachment to the T-fitting 106 can be removed by separating the two parts, or pulling the connection off the T-fitting, whereupon the T-fitting branch self-seals. This arrangement allows for the removal of the nebulizer or humidifier for (but not both) without interruption to the breathing of the patient. Removal of the nebulizer is most important and may be necessary on a routine basis to replenish the drug solution in the nebulizer.
The self-sealing T-fitting can play a critical role in the overall operation of the ventilator circuit embodiments as described herein. It is necessary to periodically remove the nebulizer from the ventilator circuit, for example, to replace it, to clean it, or to refill it. At the same time, a patient on mechanical ventilation is depending on the ventilator and the associated apparatus for their air for their lungs, which ideally is not interrupted, even for a few seconds. Accordingly, disassembling a ventilator circuit can be a problem. Removing a fitting to replace a routine must be done as quickly as possible. By the use of the spring-loaded T-fitting as described here, the nebulizer can be removed from the circuit very easily, with no interruption of air flow, and no break in the ventilator circuit.
An alternative embodiment of the ventilator circuit is shown in
This patent application claims priority to U.S. Patent Application 62/681,654, filed Jun. 6, 2018.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2019/035860 | 6/6/2019 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62681654 | Jun 2018 | US |
