CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority benefit of Provisional Application No.

63/023,073 filed on May 11, 2020, the entire contents and disclosures of which are incorporated herein by reference.

FIELD OF THE INVENTION

[0002] The present invention relates generally to the respiratory care of a patient and, more particularly, to a low cost bellows- or pneumatic-type ventilator using components available or can be easily obtained in a hospital setting, which is capable of providing ventilation support to the patient at the quality and quantity comparable to full function ventilators.

BACKGROUND

[0003] In late 2019, a novel coronavirus was identified in Wuhan province, China. The virus was later identified as SARS-CoV-2, or COVID-19, and is the cause of a current worldwide pandemic. Based on the initial Chinese data, 14%-17% of hospitalized patients required supplemental respiratory support [1, 2]. Italy was one of the first western countries with widespread disease. Their critical care facilities appeared to carry an enormous burden of the patients, with an estimated 16% of actively infected patients requiring admission to an intensive care unit (ICU) for hypoxic respiratory failure from COVID-19 [3] In the absence of definitive treatment, supportive mechanical ventilation for several days to weeks is the mainstay treatment for severe disease. [0004] Ventilation is the physiologic process of moving a gas into and out of the lungs and thereby delivering oxygen to organs of the body and excreting carbon dioxide. During spontaneous ventilation, i.e. unassisted breathing, negative (sub-atmospheric) pressure is created within the chest and gas moves into the lungs. In spontaneous ventilation exhalation is passive. [0005] In the practice of medicine, there is often a need to substitute mechanical ventilatory support for the spontaneous breathing of a patient. Mechanical ventilatory support is widely accepted as an effective form of therapy, and means for treating patients with respiratory failure or used when patients are placed under anesthesia.

[0006] Mechanical ventilatory support may be accomplished by displacing a known volume of gas into the lungs of the patient under positive pressure (any pressure greater than atmospheric pressure). Alternatively, mechanical ventilatory support may be accomplished by creating a negative pressure around the chest cavity to mimic spontaneous inhalation. While negative pressure (sub-ambient) is occasionally used for mechanical ventilatory support, positive pressure ventilation is far more common. When receiving ventilatory support, the patient becomes part of a complex interactive system, which is expected to provide adequate ventilation and promote gas exchange to aid in the stabilization and recovery of the patient.

[0007] Currently, there are approximately 62,000 full function ventilators in the United

States, with 98,000 basic ventilators, and 8,900 in the strategic reserve. The Centers for Disease Control and Prevention (CDC) estimate that between 2.4 and 21 million Americans will require hospitalization [4] Based on the Italian data [5], the number of patients requiring ventilators will range between 1.4 and 31 patients per ventilator [4] The US Department of Health and Human Services has already started to encourage rationing of ventilator use by eliminating elective surgeries [6] [0008] Due the shortage of existing ventilators, there is a critical need for a mechanical ventilatory support system that can be easily made to meet the surging demand. The design goals for the mechanical ventilatory support system of present application are as follows:

A) Components must be easily sourced “off the shelf’ items that are available to the general public;

B) The ventilatory support system of this application must have “open source” compatibility, so the design will be widely available and technically easy to build;

C) The ventilatory support system of this application be able to support a range of ventilation strategies to tolerate high airway pressures associated with Acute Respiratory Distress Syndrome (ARDS).

D) The cost of the ventilator must not be cost prohibitive.

[0009] While many modem ICU ventilators use a turbine to drive pressure, other ventilator designs have utilized servo control valves, bellows, and pneumatic pressure chambers [7, 8] The complexity of the turbine and servo control ventilators, and the sophisticated valve systems and circuitry associated with current bellows, and pneumatic ventilators, rendered them inoperable under the types of emergency conditions anticipated by the present invention.

DETAILED DESCRIPTION OF FIGURES

[0010] FIG. 1 is the schematic diagram of medical ventilator of the present invention

(Portsmouth ventilator).

[0011] FIG. 2 shows a logic diagram of control functions of the medical ventilator of present invention (Portsmouth ventilator). [0012] FIG. 3 Comparison of performance Medical ventilator of the present invention

(Portsmouth ventilator) with the DRAGER APOLLO™ (Drager, Lubeck, Germany) ventilator with ISO test numbers 1-7. Lighter waveform is airway pressure (cm FLO), and dark waveform is tracheal/alveolar pressure. Left column is the standard ventilator (DRAGER APOLLO™ (Drager, Lubeck, Germany) ventilator) and the right column is the ventilator of the present invention (Medical ventilator of the present invention).

[0013] FIG. 4 shows increasing chamber size with stable lung compliance and airway resistance (Approximate increase of 45 mL for every additional chamber added).

[0014] FIG. 5 shows effects of positive end expiratory pressure (PEEP) on tidal volumes and driving pressure.

[0015] FIG. 6 shows Airway pressure waveforms in vivo.

[0016] FIG. 7 shows pressure waveform measured at the y-piece of the breathing circuit using the medical ventilator of the present invention (Portsmouth ventilator) in vivo.

[0017]

DETAILED DESCRIPTION OF THE INVENTION

Definitions:

[0018] Tidal volume (symbol VT or TV) is the volume of air moved into or out of the lungs during a normal breath. In a healthy, young human adult, tidal volume is approximately 500 ml per inspiration or 7 ml/kg of ideal body weight.

[0019] Positive end-expiratory pressure (PEEP) is the pressure in the lungs (alveolar pressure) above atmospheric pressure (the pressure outside of the body) that exists at the end of expiration. In relation to this application, PEEP are extrinsic PEEP applied by a ventilator. [0020] Respiratory rate is the rate at which breathing occurs. This is usually measured in breaths per minute.

[0021] Inspiratory time is the time over which the tidal volume is delivered or the pressure is maintained.

[0022] Expiratory time is whatever time is left over before the next breath.

[0023] Minute Ventilation (MV) is the product of the respiratory rate and the tidal volume and provides an assessment of how much the patient is ventilating over the course of a minute.

[0024] Airway pressures are defined as the pressure in the lungs at any point throughout the respiratory cycle.

[0025] Lung compliance is the change in the volume of the lung for a given change in airway pressures. Diseased lungs typically become poorly compliant and require higher airway pressures to generate an adequate TV and MV. [0026] Peak inspiratory pressure (PIP) is defined as the highest airway pressure seen throughout the respiratory cycle. This pressure is related to the dynamic resistance of the lungs which is typically due to resistance found in the small airways of the lung.

[0027] Plateau pressure is defined as the pressure at which the lungs rest during an inspiratory effort. This pressure is related to the static resistance of the lungs which is typically due to resistance due to lung compliance and external compression of the lung.

[0028] In the United States, the standard gas pipeline pressure (wall pressure) in a hospital setting is between 50-55 PSI [9] Knowing the wall pressure, desired tidal volume breaths at set pressures may be mathematically deduced via known pressure-volume relationships. For example, under Boyle’s Law relationship (P1V1 = P2V2). PI is 50 psi (wall pressure), VI is the volume in the pressure chamber, P2 is 35 CmH20 airway pressure, and V2 is the tidal volume.

[0029] The present invention thus allows for extreme simplicity, comprises of parts easily obtained in a hospital setting with minimum modification. The medical ventilator of the present invention, comprises an oxygen containing source, at least one pressure chamber, a controller, a breathing circuit with a set of regulating valves. The flow of oxygen containing gas to the patient’s airway is regulated by three valves, such as electrically controlled solenoid valves. Respiratory rate and inspiratory time can be controlled by electronically by adjusting the timing of the valves. Tidal volume is achieved by changing the pressure chamber size through the addition or removal of expansion chambers that are attached to a primary pressure chamber. This simple design could therefore be replicated easily and reliably with few parts and easily available materials and components. [0030] Referring to FIG 1, a medical ventilator of the present invention, comprises an oxygen containing gas source 30, at least one pressure chamber 22, a breathing circuit 10 with a set of valves 21, 24, 25, 26, 29, which regulates the flow of oxygen containing breathing gas within the breathing circuit 10. Some of the valves (charging valve 21, inspiratory valve 24, expiratory valve 28) are controlled are controlled by a controller.

[0031] The oxygen containing gas source 30 supplies oxygen containing breathing gas to the medical ventilator. In one embodiment, the oxygen contain gas source 30 is a medical air supply 31 and an oxygen supply 33 at least 50 PSI. The air to oxygen ratio of oxygen containing breathing gas maybe adjusted by adjusting the respective inlets 32, 34 connected to the medical air supply 31 or the oxygen supply 33. For the prototype medical ventilator, the medical ventilator is connected to pipeline air and oxygen supply. Both air and oxygen source delivers gas at least 50 PSI. The air to oxygen ratio of the breathing gas delivered to the pressure chamber 22 may be adjusted by turning the inlet to the air supply 32 and the inlet to the oxygen supply 34. For example, if only inlet to the oxygen supply is open, breathing gas containing 100% oxygen is delivered to the pressure chamber 22. If only medical air inlet is turn on 32, a breathing gas containing 21% oxygen is delivered to the pressure chamber 22. If both medical air inlet 32 and the oxygen supply inlet 34 is turn on, a breathing gas containing 60% of oxygen is supplied to the pressure chamber 22. In another embodiment, a gas blender 35 may be connected in between the medical air inlet 32 and oxygen inlet 34, and the pressure chamber to allow thorough mixing of the breathing gas mixture.

[0032] The desired tidal volume can be adjusted by adding or removing inter-connectable expansion pressure chambers 23 to the primary pressure chamber 22. For example, in the prototype ventilator, the addition of a single extension generates approximately 45 mL of additional tidal volume in a physiologically normal adult lung. The breathing gas is delivered to the charging pressure chambers at 50-55 PSI by opening the charging valve 21 for a set period of time. Using a Boyle’s Law relationship (P1V1 = P2Y2), the pressure chamber volume at high pressure is discharged into the breathing circuit, and in turn into patient’s lung, which is at a lower pressure and a higher volume. In one embodiment, the pressure chamber is expandable with adjustable segments, to accommodate different sized patients. The charging valve opens at a frequency and for a time period controlled by the controller 40, which may be adjusted by the user. In one embodiment, the charging valve opens between every breath (respiratory cycle), and stays open for 100msec. Its timing is dependent on the respiratory rate.

[0033] The breathing circuit 10 of the present invention is in fluid communication with the pressure chamber 22 at a first end 14 and conveying a flow of oxygen containing breathing gas from the pressure chamber 22 to the breathing circuit 10, which is controlled by an inspiratory valve 24. The breathing circuit 10 connectable at a second end 16 to a breathing tube insertable into a patient, such as an endotracheal tube, conveying the flow of oxygen containing breathing gas to the patient. The breathing circuit 10 is also in fluid communication with ambient air at a third end 15, which release gas from the breathing circuit, including expiration from the patient into the ambient air, which is controlled by an expiratory valve 28 and a PEEP valve 29. The charging valve 21, the inspiratory valve 24 and expiratory valve 29 are controlled by a controller, via which the user can adjust respiratory rate and inspiratory time. Although many type of gas valves may be used as the charging valve 21, the inspiratory valve 24 and expiratory valve, in the prototype medical ventilator, electric solenoid valves are used.

[0034] In an embodiment of the medical ventilator, the breathing circuit 10 comprises an elongated main tube 11 having a bore completely therethrough, which is connectable at a first end 16 to a breathing tube insertable into a patient, conveying the flow oxygen-containing breathing gas into a patient's airway. The breathing circuit 10 further comprises an inspiratory tube (inspiratory limb) 12 that is connected to the main tube at a first end 14 and pressure chamber at other end 17. The inspiratory tube has a bore completely therethrough and is in fluid communication with the main tube bore 11 and the pressure chamber 22 via inspiratory valve 24. The breathing circuit 10 further comprises an expiratory tube (expiratory limb) 13 that is connected to the main tube at the first end 18 and to ambient air. The expiratory tube 13 has a bore completely therethrough and is in fluid communication with the main tube bore and ambient air via expiratory valve 28 and PEEP valve 29 at the other end 15.

[0035] The controller 40 of present invention may be any computing device, including but not limited to a mobile computing device, a computer or a microcontroller. The controller 40 receives continuous pressure measurements of the breathing circuit, which is measured by one or more pressure sensor 27, such as a transducer on the breathing circuit 10. The controller 40 regulates operation of the charging valve 21, the inspiratory valve 24 and the expiratory valve 28, which is set by a user according to the desirable respiratory rate, inspiratory time. The charging valve 22 opens at a rate set by an external rheostat of between 3 to 30 times per minute to achieve a predetermined tidal volume set approximately at between 350-1500 ml. This was the amount of time needed to fully charge the pressure chamber. In one embodiment, the inspiratory valve 24 is closed for 100 milliseconds prior to re-opening the charging valve 21 and both the charging 21 and inspiratory 24 valves are never actually open at the same time.

However, it is still prudent to open the charging valve 21 for as short a period as possible to minimize the patient’s potential exposure to the pipeline pressure (in case inspiratory valve failed to close). [0036] The inspiration valve opens and the expiratory valve closes at a predetermined respiratory rate for a preset inspiratory time. During expiratory time, the inspiratory valve is closed and the expiratory valve opens. The expiratory valve opens into a positive end expiratory pressure (PEEP) valve, the PEEP valve 29 maintains pressure within said breathing circuit during expiration at approximately between 0-20cm EhO and PEEP may be delivered to the patient if pressure is outside this range.

[0037] In one embodiment, the respiratory rate is set at approximately 4-30 breath per minutes (BPM) and the inspiratory time is set at approximately 0.5- 7.5 seconds. The maximum circuit pressure (or airway pressure) is set at approximately 35 35 cmTbO. The tidal volume is maintained at approximately 350-1500 mL and oxygen concentration of the breathing gas is set at approximately, 21-100%. These exemplary performance range of a medical ventilator of the present invention is shown in Table 1.

Table 1. Ranges of Values for Performance of the Ventilator

[0038] In one embodiment, the medical ventilator further comprises at least one pressure sensor 27, such as a pressure transducer. The pressure sensor 27 continuously measure the pressure within the breathing circuit and communicating these pressure measurements to the controller 40. In the prototype medical ventilator, the pressure transducer periodically transmits pressure measurements of the breathing circuit to the controller 40, which the controller uses to control the operation of charging valve, inspiratory valve or the exploratory valve. In another embodiment, the medical ventilator of the present invention further comprises one or more warning lights that are controlled by said controller, which display different warning lights when pressure of the breathing circuit from 0 to 15 cmH20, from 15 to 30 cmH20, or greater than 30 cmH20 for a predetermined period.

[0039] The medical ventilator may further comprises additional safety features. In one embodiment the medical ventilator comprises a pressure relief valve 26 on the inspiratory tube, which releasing oxygen containing breathing gas from the breathing circuit into ambience air when pressure within the breathing circuit exceeding 0.5 psi (35cmH20). In another embodiment, the medical ventilator further comprises a negative pressure relief valve 25 on the inspiratory tube, which to allow for spontaneous room air inspiration at any point during the respiratory cycle to prevent a negative pressure injury when the pressure within the breathing circuit is below 0 PSI. The medical ventilator may further comprises an alarm 41. The alarm 41 is turn on by the controller when pressure within the breathing circuit is less than 3cmH20 for a prolonged period warning user to check the medical ventilator for disconnections or faulty gas supply.

[0040] In the prototype embodiment, the ventilator displays a green LED light for airway pressures from 0 to 15 cmH20, an amber LED light for airway pressures from 15 to 30 cmH20, and a red LED light for airway pressures for greater than 30 cmH20. Should a prolonged period (such as 5 seconds) of “red” pressures be identified, the medical ventilator will allow for a prolonged expiratory phase. The ventilator will not deliver (closing charging valve) additional breaths if the airway pressure remains high. Should the ventilator detect a prolonged period (such as 20 seconds) of airway pressures < 3 cmH20, it will generate an alarm that indicates either a loss of fresh gas supply or disconnection of the breathing circuit from either the inspiratory or expiratory limbs or from the endotracheal tube itself.

[0041] The logic diagram of the prototype control algorithm is shown on FIG. 2. The main program periodically samples airway pressure and monitors for prolonged periods of high or low airway pressures (pressure within breathing circuit). High and low-priority interrupts are programmed to handle timing of solenoid opening and closing throughout the respiratory cycle. They also control the holding open of the expiratory valve in the event of prolonged, elevated airway pressure, the other safety feature built into the medical ventilator.

[0042] As shown in FIG. 2, T_High and T_Low are protective measures designed to alert the user to potentially dangerous malfunction of the ventilator. T High alerts and decompresses the airway when the pressure is above the P High threshold (around 30 cmH20 in the prototype) for a period of time. For example, if the airway pressure (pressure within breathing circuit) were to stay that high for an extended period of time, it could indicate the expiratory valve malfunctioned is stuck at the closed position. Airway pressure above the 35 cmH20 is released by the pressure relief valve 26, which should protect patient when this occurs. Alternatively, there could be a problem with the charging and inspiratory valve timing or function that could be exposing the patient to pipeline pressure of 50 psi. While in some clinical situations increased airway pressure is helpful, the degree of increased airway pressures that would trigger this alarm could easily cause injury (barotrauma) to the patient. In the prototype, alarm is set at 5 seconds for this accounts for the longest inspiratory time that is clinically reasonable, while minimizing the amount of time that the patient would be exposed to potentially dangerous airway pressures. T High is 5 seconds by default and can be modified to 20 seconds.

[0043] The T Low alarm is not necessarily immediately dangerous to the patient and is meant to detect either circuit disconnect, a disconnection or failure of wall gas supply, or some problem with the charging or inspiratory valves. Because low pressures are not immediately dangerous, T_low is set at 20 seconds as low airway pressures.

[0044] When using a medical ventilator of the present invention to delivering a flow of oxygen-containing gas to the airway of a patient. The user must first connects a patient’s breathing tube to the patient’s airway and to the oxygen containing gas source. The user can then adjust and set air to oxygen ratio of the breathing gas, which is supplied by the oxygen containing gas source. The user then determines and sets the desirable tidal volume for the patients by adding or removing expandable interconnected pressure chambers. The patient’s respiratory rate, inspiratory time is set by adjusting these parameter on the controller. Finally, the user can turn on the gas source and the controller, and starts delivering oxygen-containing gas to the patient. When pressure within the breathing circuit is less than ScmFhO for a prolonged period, an alarm will be sounded and the user need to check gas source, breathing circuit, and breathing tube for leaks or disconnections

Although the components of the prototype medical ventilator is built using commercial off the shelf components or parts readily amiable in a hospital setting. Some of the components may be manufactured via 3-D printing or additive manufacturing, which is widely known in the art. Standard materials, like plastics and metals, and advanced polymers and composites can all be 3D printed with various processes. Most materials fall into one of the four categories displayed below. Table 4 materials used for 3-D printing

Material

Printing Considerations Applications

Type

Available as powder suspensions; require Aerospace, automotive, tooling,

Metals heat/light for curing refractory metal components

Uses a powder/binder mix or slurry with Machinery, electronics, biomedical

Ceramics specialized processes for printing engineering, and aerospace

Uses extrusion processes; mechanical Small and medium-sized mechanical properties can be tuned, but the material is parts with high strength-to-weight

Composites less adaptable to multiple printing ratio; unique applications like building processes materials

Many materials with a broad range of

Footwear, dental devices, tooling, Polymers mechanical properties, adaptable to wearable products, medical products multiple printing processes

Example 1 : Prototype low cost ventilator of the present invention

[0045] All of these components may be exchanged for compatible components with little to no modification in the event of component unavailability or unacceptable lead-time. It is appreciated that the hardware components of the current design maybe readily replaced with other comparable parts, such as components with smaller footprints (e.g., using surface-mount packages instead of larger, through-hole packages). The prototype as tested, is fully functional and compact.

[0046] In an embedment of the present invention, the ventilator hardware is built on a 4- layer printed circuit board with dimensions of about 2.5 x 3 inches. It is powered by a 12V DC wall adapter. The microcontroller (Microchip PIC 18F27K42, Microchip Technology Inc., Chandler, A Z, USA) is a high-performance 8-Bit MCU. It is chosen for its low cost (under $2), built-in peripheral functions, fast and hierarchical handling of interrupt service routines, and overall availability and open source support. The microcontroller provides up to 12-bit analog to digital conversion with multiple channels, high frequency internal oscillator to drive instructions for fast processing, and USART capability for data transmission, among several other powerful capabilities. However, most modem day microcontrollers would provide adequate capability with appropriately written software. The microcontroller was programmed with MICROCHIP’S™ MBPLAB X IDE (Microchip Technology Inc., Chandler, AZ, USA). This development environment supports PERIPHERAL PIN SELECT ™, allowing the user to assign specific peripheral functions, such as the analog to digital conversion inputs, to specific pins on the microcontroller to improve hardware design.

[0047] Gas pressurization and flow are controlled by three 12V solenoid valves. These valves open and close with precise timing to allow safe and effective ventilation. Three of the microcontroller output pins are connected to logic-level MOSFET transistors, allowing rapid switching of the solenoids on and off with timing specified by the user. The timing is controlled by two rotary potentiometers the user adjusts to set respiratory rate and inspiratory time.

[0048] Gas pressures in the breathing circuit is measured by a pressure transducer rated for +/- 0.5 PSI (24PCEFA6G, Honeywell International Inc., Charlotte, NC, USA), or roughly +/- 35 cmH20. This pressure is sampled at a rate of 8Hz and is transmitted via serial protocol to an external computer, although this could be modified to use Bluetooth for wireless capability. Of note, this data transmission is useful for viewing airway pressure waveforms but is unnecessary for overall ventilator function. The microcontroller continuously illuminates one of several LEDs that correspond to specific pressure levels, providing the user with visual feedback on airway pressures throughout the respiratory cycle without the need for a display screen. A safety feature is built into the ventilator when pressure exceeds a specific threshold for a set period of time, ventilation will cease and the expiratory valve will remain open until pressure falls below a specific threshold, and then ventilation will resume. The thresholds and time periods may be modified with modification to the program.

EXAMPLE 2: TESTING OF THE PROTOTYPE MEDICAL VENTILATOR [0049] It is hypothesized that the present invention would be comparable to the standard- of-care ventilators, while still meeting the design requirements described. Both in vitro and in vivo testing of the prototype ventilator were carried out.

[0050] In simulated lung testing, the performance of the prototype ventilator was assessed through the demonstration of International Organization for Standardization (ISO) ventilator testing, and of equivalent pressure-volume and flow relationships during ventilation in both normal and pathologic lung models. In live-tissue models, the performance of prototype ventilator was to be assessed by the demonstration of adequate oxygenation and ventilation through comparative blood gas analysis.

A. Simulation Testing:

[0051] Human lung simulation was achieved using the ASL 5000™ respiratory simulator

(IngMar Medical, Pittsburg, PA, USA). Compliance and resistance testing was preformed using procedure similar to the process described by Cristiano et al [10], which is hereby incorporated by reference. The prototype ventilator of present invention was compared with a commercially available ventilator (DRAGER APOLLO ^® , Drager, Inc., Lubeck, Germany) in both pressure control (P-CMV) and volume control (VC-CMV). Three initial trials were completed with the following lung parameters settings:

1) Resistance 12 cmH20/L/s and compliance 20 mL/cmH20 2) Resistance 12 cmH20/L/s and compliance 50 mL/cmH20

3) Resistance 15 cmH20/L/s and compliance 50 mL/cmH20.

[0052] These simulations represent states of low compliance with normal airway resistance, normal lungs, high airway resistance and normal compliance respectively. Waveform data from these simulated tests are displayed in FIG. 3.

[0053] The prototype ventilator was further tested with varying degrees of airway resistance and lung compliance to simulate severe ARDS and Chronic obstructive pulmonary disease (COPD) based on existing literature for lung respiratory parameters [11-14] Similarly, we tested extremes of compliance and resistance to further validate the range of pathophysiologic states over which the ventilator can safely operate. This included extremely low compliance with high resistance, extremely high compliance with low resistance, and varying high/low combinations of compliance and resistance. Due to lack of ISO standards for tidal volume predictability in ventilators that are neither traditional volume control nor pressure control, an arbitrary +/- 10% range was set from predicted tidal volume in the trial. This is clinically appropriate as it represents less than 1 mL/kg deviation. Because of the large pressure differences in the pulmonary system compared with the pipeline/charging cylinder (20cmH2O is equivalent to 0.284 PSI), we assumed the predicted tidal volumes would remain nearly constant over a range of compliance, resistance, and PEEP variables.

[0054] To be thorough, other examples of ventilator testing were included [15, 16]

Based on these, we similarly followed the previously described protocol to perform testing at resistance of 5 cmH20/L/s and compliance of 100 mL/cmH20, resistance of 20 cmH20/L/s and compliance of 30 mL/cmH20 (ARDS), and resistance of 50 cmFLZO/L/s and compliance of 100 mL/cmH20 (obstruction)! 5. We followed the additional protocol comparing resistance of 5, 10, and 20 cmH20 with compliances of 30, 70, and 120 mL/cmH2016. These data are summarized in Table 2.

Table 2. Average Tidal Volume Delivery with Varying Pulmonary Mechanics, Predicted

520 mL Tidal Volume [0055] Testing revealed strongly predictable tidal volumes all within the acceptable 10% change from baseline. Poorly compliant mechanics were associated with higher plateau pressures and lower tidal volumes, though the ventilator still performed within the standard.

[0056] Other testing is summarized in FIG 4, which describes the impact of adding pressure chamber expansions to the main pressure chamber on tidal volume, while FIG 5 demonstrates the minimal effect of PEEP on the driving pressure needed to generate these tidal volumes. There was a theoretical concern that the tidal volume delivered might increase in a non-linear manner due to increased airway pressure, but the stepwise volume increases appear to operate in a linear manner across physiologic pressure ranges (R2 = 0.999). This simulated testing suggests that the proposed mechanism of changing the size of the pressure chamber through the addition or removal of smaller expansion chambers is a reliable and predictable means of modifying the tidal volume that is being delivered to a patient. It also suggests that the prototype ventilator is able to deliver these tidal volumes at airway pressures that are comparable to other commonly used ventilators.

[0057] An additional high fidelity lung simulator (TestChest, Organis GmbH, Landquart,

Switzerland) was used for further simulation testing. ISO standard for volume control ventilators was accomplished with trials 1-717. The ventilator was tested against the simulated COVID-19 in the lung model. Two models were used, an early model and a late/severe model. The early was characterized by chest wall compliance of 93 mL/hPa, total compliance 52 mL/hPa, and airway resistance 5, while the late model had a chest wall compliance of 93 mL/hPa, total compliance 39 mL/hPa, and airway resistance 5. This was also tested against the standard ventilator, with volume control mode compared to the prototype ventilator. [0058] In summary, the performance of the ventilator of present invention was similar to existing ventilators across a range of pulmonary mechanics. Changes in PEEP and tidal volumes did not impact predicted tidal volume delivery. There was no apparent change between airway resistances, and pulmonary compliance. There is a decrease tidal volume delivery, but the ventilator was still able to deliver adequate tidal volume breaths. The major difference between the Medical ventilator of the present invention and the existing ventilator was a very transient elevation in the initial airway pressure while the chamber was first decompressing. This is due to the decompression from the high pressure chamber, and it appears that the compliance of the breathing circuit, endotracheal tube, and larger airways absorbed this impulse, sparing the smaller airways and alveoli. This is consistent with our calculated pressures and appears to be safe for in vivo use.

B. In Vivo Testing

[0059] The in vivo study was approved by the Naval Medical Center Portsmouth

Institutional Animal Care and Use Committee (IACUC) under protocol number NMCP.2020.0011. A single female 84kg Yorkshire swine was used for testing. The animal was anesthetized with IM ketamine, acepromazine, and atropine, and placed on 100% Fi02 with 2% isoflurane until intubation. The animal model remained on 100% Fi02 throughout the study period. Following intubation, the animal was then transitioned to a total intravenous anesthetic with fentanyl and propofol. The animal was maintained on a standard veterinary mechanical ventilator throughout induction (Hallowed EMC Model 2000, Hallowed EMC, Pittsfield, MA, USA). The animal was paralyzed with rocuronium that was titrated 1 of 4 train-of-four twitches. [0060] Following induction, the animal was maintained on the standard veterinary

Hallowed ventilator for 60 minutes. At t=60, the animal model was transitioned to the Medical ventilator of the present invention, and mechanical ventilation was provided for an additional 120 minutes. Arterial blood gas measurements were collected and pH, p02, and pC02 are recorded at t=0, t=15, t=30, t=45, t=60, t=75, t=90, t=105, t=120, t= 135 , t=150, t=165, t=l 80, where t=0 corresponds to placement of the arterial line immediately following intubation. Therefore, samples up to and including t=60 reflect standard ventilator function, and all samples beginning at t=75 reflect the Medical ventilator of the present invention. Pulse oximetry and end- tidal C02 readings were also recorded at these intervals. Airway pressures were monitored and recorded by an external pressure sensor at 60Hz, in addition to the sensor in the ventilator. After t=180, the animal was euthanized per standard veterinary protocols.

[0061] Throughout the study period, the respiratory parameters of Medical ventilator of the present invention were manipulated by the investigators to provide optimal ventilation, and then to test its maximal capabilities through “stress-testing” where the respiratory rate was increased sequentially in an effort to determine the threshold at which the ventilator would no longer provide safe or effective ventilation. These parameters were changed every 15 minutes corresponding with the scheduled arterial blood gas analysis. The respiratory parameters that are reported are correlated to the blood gas analysis that was obtained 15 minutes after the ventilator settings were changed (summarized in Table 3). This allows an adequate period of equilibration following the modification of ventilator settings. Blood gas analysis that is reported accurately reflects the physiologic state induced in the animal model as a direct result of the reported ventilator settings. It should be noted that the patient remained hemodynamically stable throughout the study period. Table 3. Relevant Ventilator Settings and Measures of Ventilation during Porcine Testing

[0062] RR = Respiratory Rate; TV = Tidal Volume; PEEP = Positive End Expiratory Pressure; Pa02 = Arterial oxygen tension; EtC02 = End tidal C02 partial pressure; PaC02 = Arterial C02 tension; Sp02 = Arterial oxygen saturation.

[0063] FIG. 6 shows the airway pressure waveforms during in vivo testing. Pressure waveforms measured at the y-piece of the breathing circuit. The shorter (blue) tracing is the standard ventilator. The taller (red) tracing is the Medical ventilator of the present invention. These two tracings were recorded within 10 minutes of each other, immediately before and after t=60 when we changed ventilators.

[0064] FIG 7. Shows pressure waveform measured at the y-piece of the breathing circuit using the Medical ventilator of the present invention in vivo testing. Recorded toward the end of the study using 7 expansion chambers (tidal volume approximately 705cc, or 8.4cc/kg) and 10 cmH20 PEEP. The tracing shows the brief pressure impulse immediately following chamber depressurization. Sampling here was 60Hz, and discrete analysis shows only one data point at each of the pressures above 20 cmH20, suggesting that the pressure exceeded 20 cmH20 for 33 milliseconds or less.

[0065] During this testing, the Medical ventilator of the present invention was able to provide adequate ventilation to the 84 kg swine model. Indeed, during the sequential “stress testing” of the Medical ventilator of the present invention, the investigators were able to hyperventilate the subject to a PaC02 of 35.5 mmHg without device failure.

[0066] Other points of interest include the apparently lower EtC02 to PaC02 gradient that was generated while using the Medical ventilator of the present invention when compared to the conventional ventilator. The mean difference of these values was significant based on a 2- sided t-test with p< 001. This suggests there was an enhanced open lung ventilation strategy [18] when using the Medical ventilator of the present invention when compared to the veterinary ventilator. We theorize that this finding is due to the inability of the veterinary ventilator to administer PEEP. The use of PEEP in modern ventilators has been well documented to improve the gradient and is a critical function [19, 20] The use of a PEEP valve in the Medical ventilator of the present invention and the application of PEEP to this swine model resulted in the decrease in apparent dead space ventilation that was seen in this study.

[0067] The Medical ventilator of the present invention provides a hybrid, pneumatic form of intermittent mandatory ventilation. It is also functionally capable of providing synchronized intermittent mandatory ventilation without any change to existing hardware, though software support for this functionality is still in development. Inspiratory airway pressure in this ventilator is limited to 35 cmH20 by default through the use of a fixed mechanical pressure release within the inspiratory limb of the breathing circuit that will vent airway gas to the atmosphere if its pressure increases above 35 cmH20. During simulated testing on physiologically normal lungs, the peak airway pressures tended to be higher than recommended (<2 cmH20), albeit for extremely brief periods of time (33 milliseconds or less). Plateau pressures were normal, and both simulators that were used showed that that pressure spike was not propagated to the level of the trachea, distal airways, or alveoli. Given the extremely transient duration and lack of propagation to distal airways, this is of uncertain physiologic significance. The simulation of pathologic states of increased airway resistance caused this peak pressure to be correspondingly greater than the plateau pressure. This is an expected physiologic change, and does not likely represent increased danger to the patient. Pending further analysis and review, if this is determined to be significant, very simple modification of the pneumatic design will allow dampening of the impulse.

[0068] This system utilizes a PEEP valve that is commonly available within hospital systems to provide PEEP with a bag-valve-mask set up. Most patients in the ICU who are mechanically ventilated will have a bag-valve-mask system at the head of the bed, and the majority of these in a clinical setting incorporate a PEEP valve. This system leverages this PEEP valve to provide PEEP to the ventilator. By removing the PEEP valve from the bag-valve-mask and applying it to the Medical ventilator of the present invention, its use is extended and the ventilator is able to provide from 0 to 20 cmH20 of PEEP in a continuous interval.

[0069] Through the use of a rheostat (variable resistor) that is incorporated into the circuit diagram, the inspiratory to expiratory (I:E) ratio is able to be adjusted from 1 : 1 to greater than 1 :5 in the setting of very slow respiratory rates. Likewise, through the adjustment of a second rheostat, the respiratory rate can be set from 4 to 30 breaths per minute. Adjustment of tidal volume is slightly more abstract, but by adjusting the number of smaller pressure expansion chambers that are attached to the primary pressure chamber, the tidal volume of this ventilator can be adjusted from 300 mL to 800 mL tidal volumes in 45 mL increments.

[0070] The Medical ventilator of the present invention connects to the wall pipeline air and oxygen supplies using diameter index safety system (DISS) connectors that are standardized throughout the United States, though these could easily be changed for the local standard connectors wherever this ventilator is needed. By design, this ventilator has a gas reservoir that allows for peak inspiratory flow rates of up to 120 liters per minute despite the average wall pipeline oxygen supply only providing around 6 - 10 liters per minute. The proportioning system is able to provide 50-60% Fi02 in addition to 90-100% Fi02 options through mixing of wall pipeline air and oxygen within the gas blender portion of the ventilator. This ventilator also allows for the use of standard connectors to ISO 5356-1:2015.

[0071] A commercially available lithium-polymer battery can provide up to 30 minutes of backup function in case of failure of the main electrical system. Otherwise this system is powered by a US standard 120-V 3 pin plug (this does not meet the UK standard, though could be easily converted to allow for a 240V to 12V conversion) using a 12V DC converter. The circuit can be modified to include an on-board voltage regulator to provide 12V DC with other, more commonly available, power sources such as a standard laptop charger.

[0072] This ventilator provides an auditory and visual alarm in the event of gas supply failure by detecting whether minimal inspiratory pressures are not achieved for a designated period of time. It also provides auditory and visual alarms in the setting of electricity supply failure should the battery backup be required. Given the nature of the ventilator, it is largely impossible to determine if the tidal volume is exceeded. However, if there is a prolonged period of dangerously elevated airway pressures, the ventilator will enter a fail-safe mode. In this mode, an auditory alarm will sound and the ventilator will vent the breathing system through the expiratory valve and not resume ventilation until the airway pressures return to lower than 15 cmH20.

[0073] As mentioned previously, this ventilator shows the airway pressure in a categorical fashion, with pressures from 0 - 15 cmH20 powering a green LED, pressures from 16 - 30 cmH20 powering an amber LED, and pressures above 30 cmH20 powering a red LED. While this does not provide the granularity of a digital display, it is simpler and cheaper, and still provides sufficient information to guide ventilator management. The setting of tidal volume is visualized by the number of expansion chambers that are added to the primary pressure chamber. The setting of respiratory frequency is visualized by the physical position of the rheostat that controls the respiratory rate. Fi02 is visualized by either having solely the oxygen valve open or having the medical air valve open in the gas blender as well. If both valves are open, the Fi02 is from 50-60%, while if only the oxygen valve is open the Fi02 is from 90-100%. References

1. Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID- 19 in Wuhan, China: a retrospective cohort study. The Lancet vol. 395 1054-1062 (2020).

2. Wu, Z. & McGoogan, J. M. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA (2020) doi:10.1001/jama.2020.2648.

3. Grasselli, G., Pesenti, A. & Cecconi, M. Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response. JAMA (2020) doi : 10.100 l/jama.2020.4031.

4. Truog, R. D., Mitchell, C. & Daley, G. Q. The Toughest Triage — Allocating Ventilators in a Pandemic. New England Journal of Medicine (2020) doi: 10.1056/nejmp2005689.

5. Sorbello, M. et al. The Italian coronavirus disease 2019 outbreak: recommendations from clinical practice. Anaesthesia (2020) doi: 10.1111/anae.l 5049.

6. News Division. Optimizing Ventilator Use during the COVID-19 Pandemic. HHS.gov https://www.hhs.gov/about/news/2020/03/31/optimizing-ventila tor-use-during-covidl9- pandemic.html (2020).

7. Thille, A. W., Lyazidi, A., Richard, J.-C. M., Galia, F. & Brochard, L. A bench study of intensive-care-unit ventilators: new versus old and turbine-based versus compressed gas- based ventilators. Intensive Care Med. 35, 1368-1376 (2009).

8. Williams, D., Flory, S., King, R., Thornton, M. & Dingley, J. A low oxygen consumption pneumatic ventilator for emergency construction during a respiratory failure pandemic. Anaesthesia 65, 235-242 (2010). Nfpa. Nfpa 99: Health Care Facilities Code, 2012 Edition. (2011). Cristiano, G. et al. Mechanical Ventilator Milano (MVM):A Novel Mechanical Ventilator Designed for Mass Scale Production in response to the COVID-19 Pandemics. doklO.l 101/2020.03.24.20042234. Amal, J.-M., Garnero, A., Saoli, M. & Chatbum, R. L. Parameters for Simulation of Adult Subjects During Mechanical Ventilation. Respir. Care 63, 158-168 (2018). Kathleen A Davis, Heather P Peterson, Alex R Sanders and Lonny Ashworth. A Bench Study Evaluation of the Amount of AutoPEEP When Ventilating an Electronic Lung Model Simulated to Represent Normal, ARDS and COPD Conditions. Respir. Care 64, (2019). Ferreira, J. C., Chipman, D. W., Hill, N. S. & Kacmarek, R. M. Bilevel vs ICU ventilators providing noninvasive ventilation: effect of system leaks: a COPD lung model comparison. Chest 136, 448-456 (2009). Beydon, L., Svantesson, C., Brauer, K., Lemaire, F. & Jonson, B. Respiratory mechanics in patients ventilated for critical lung disease. European Respiratory Journal vol. 9 262-273 (1996). Boussen, S., Gainnier, M. & Michelet, P. Evaluation of ventilators used during transport of critically ill patients: a bench study. Respir. Care 58, 1911-1922 (2013). L’Her, E , Roy, A. & Marjanovic, N. Bench-test comparison of 26 emergency and transport ventilators. Crit. Care 18, 506 (2014). International Organization for Standardization. Medical electrical equipment Part 2-12: Particular requirements for basic safety and essential performance of critical care ventilators. (02-2020). Hodgson, C. L. etal. A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome. Crit. Care 15, R133 (2011). Murray, I. P., Modell, J. H., Gallagher, T. J. & Banner, M. J. Titration of PEEP by the arterial minus end-tidal carbon dioxide gradient. Chest 85, 100-104 (1984). Blanch, L., Fernandez, R., Benito, S., Mancebo, J. & Net, A. Effect of PEEP on the arterial minus end-tidal carbon dioxide gradient. Chest 92, 451-454 (1987). Medicines and Healthcare products Regulatory Agency. Rapidly Manufactured Ventilator System. (2020).