Ventilator: Demystified

<Content is from my patent/s last year post Covid-19 outbreak when I made all inventions open-sourced with an intent that anyone can create and mass-produce simple life saving machines>

Background

The world faces a severe and acute public health emergency due to the ongoing COVID-19 global pandemic. How individual countries respond in the coming weeks will be critical in influencing the trajectory of national epidemics. COVID-19 can require patients to be on ventilators for significant periods of time, meaning a hospital can only accommodate so many patients at once.

About 880,000 more ventilators will be needed to deal with the demand caused by the coronavirus outbreak globally, according to new analysis. Analytics company GlobalData estimates the US needs about 75,000 ventilators, while France, Germany, Italy, Spain and the UK collectively require 74,000 devices to make up the gap (14).

It’s estimated that, of the Covid-19 cases occurring worldwide, about 10% of patients need ventilators. GlobalData’s medical devices analyst Tina Deng said: “Ventilator shortages are a crucial reality as the Covid-19 outbreak continues to worsen globally.

There are not enough ventilators available in hospitals right now for all of the potential patients who will be struck by the virus. An influential report from Imperial College London estimates that 30% of Covid-19 hospitalised patients are likely to require mechanical ventilation. The only way to avoid overwhelming intensive care units, it says, is with a mandatory lockdown that reduces social contact by 75%

Plus, ventilators are expensive pieces of machinery to maintain, store and operate. They also require ongoing monitoring by health-care professionals (15).

Analysis on Medical Infrastructure to handle an epidemic :

1 . Number of beds : For patients who are found to be COVID-19 positive, isolation wards are needed; additionally, for critical cases, intensive care is needed. Currently, almost all suspected cases of coronavirus are referred to government hospitals and it’s important to assess where we stand in terms of medical capacity to provide necessary healthcare to the affected individuals.

? Total government hospital beds in India (1) = 713,986

? Population of India (2) = 1,360,000,000

? Number of Beds per 1000 People = 0.525

?  Taking into account vulnerability of COVID-19, Number of people above 45 years of age (28% of total population) = 380,800,000

? Assuming 5% of vulnerable people fall ill = 19,040,000

? Number of Beds per 1000 Vulnerable People = 37.49

2 . Number of Ventilators : 7,13,986 total government beds, out of which 5-8% are ICU beds (35,699 to 57,119 ICU beds) (3)

? Assuming that 70% of these ICU beds have ventilators, we arrive at an estimate of 24,989 to 39,983 ventilators.

? Even if we consider 100% of ICU beds are equipped with ventilators, we have a maximum of 57,000 ventilators.

? As per WHO, 16% (1:6) people undergo critical stage and require ventilator, As of which number of people requiring ventilator = 3,046,400

? Number of Ventilators per 1000 Vulnerable people = 18.71

 3. Viability of an Industrial ICU Ventilator : 10,000 ventilators are on-order with cost of ventilator = Rs. 380,000 each.

? Total cost involved in order of ventilators = Rs. 3,800,000,000

? In total, 67000 number of Ventilators after procurement

? Number of Ventilators per 1000 people after procurement = 21.99

? Even after spending 380 Crores, we are short of 978 ventilators per 1000 people to handle an epidemic in its full capacity.

? As per the sources and similar Medical Infrastructure capacity, British Medical Association suggested that younger, healthier people could be given priority over older people and that those with an underlying illness may not get treatment that could save them, with healthier patients given priority instead. (5)

 4 . Number of physicians : Over 11.57 lakh Allopathic doctors (6) are registered with the State Medical Councils and the Medical Council of India.

? Assuming 90% availability, it is estimated that around 1,041,300 doctors may be actually available for active service.

? Number of Doctors per 1000 People = 0.765

? Which is lower than the World Health Organisation norm of 1:1000

? Besides, there are 7.88 lakh Ayurveda, Unani and Homeopathy (AUH) doctors in the country. Assuming 80% availability, around 630,000 may be available for service. It gives a Doctor Population Ratio of 1.22 per 1000 people.

? As per As per Indian Nursing Council (INC) records, there are around 30.4 lakh nursing personnel registered in the country as on December 31, 2018.

? Assuming 80% availability, it is estimated that around 2,432,000 nursing personnel are available for active services, which gives a Nurse- Population Ratio of 1.788 per 1000 people against WHO norms 3:1000.

Genetic Analysis of SARS-CoV-2 :

 In these severe cases, the virus causes damage to the lungs. The body's immune system detects this and expands blood vessels so more immune cells enter. But this can cause fluid to enter the lungs, making it harder to breathe, and causing the body's oxygen levels to drop.

 Analysis of the genetic template for the spike proteins that protrude from the surface of the SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus-2) show that the "hook" part of the spike had evolved to target a receptor on the outside of human cells called ACE2 (Angiotensin-converting enzyme 2), which is involved in blood pressure regulation. (7)

 Angiotensin-converting enzyme 2 (ACE2) (8) is an enzyme attached to the outer surface of cells in the lungs, arteries, heart, kidney, and intestines. As a transmembrane protein, ACE2 serves as the main entry point into cells for SARS- CoV-2.

 To alleviate this, a normal ventilator is used to push air, with increased levels of oxygen, into the lungs, Ventilator which also has a humidifier, adds heat and moisture to the medical air so it matches the patient's body temperature. Patients are given medication to relax the respiratory muscles so their breathing can be fully regulated by the machine.

Why and When Ventilator :

When your lungs inhale and exhale air normally, they take in oxygen your cells need to survive and expel carbon dioxide. COVID-19 can inflame your airways and essentially drown your lungs in fluids. A ventilator mechanically helps pump oxygen into your body. The air flows through a tube that goes in your mouth and down your windpipe. The ventilator also may breathe out for you, or you may do it on your own. (19)

When would a patient go onto a ventilator

A normal breathing rate is about 15 breaths a minute, if the rate gets to about 28 times a minute, then this is a signal of respiratory failure that ventilation may be needed.

How soon might a patient need a ventilator and for how long

The patient can be sustained for short periods of time using manual forms of ventilation such as using a bag and mask system with oxygen, but usually being attached to a ventilator needs to happen within 30 minutes if critical. A patient may need to be on a ventilator for weeks to deliver smaller volumes of oxygen and air, but at higher rates.

Why a shortage of ventilators matters

(9) This means that many will not be able to be treated with mechanical ventilation and difficult decisions will have to be made by staff, families and patients about the limits of support.

How do ventilators help patients breathe

BREATHING PRESSURES OF NORMAL AND ABNORMAL PATIENTS

Doctors monitor patient breathing rates per minute:

A popular mode used with ventilators is called assist-control (AC). In that mode, the ventilator assists with breathing. It's ideal for recovery because the patient only has to initiate a breath and the ventilator does the rest.

INHALE AND EXHALE PRESSURE DIFFERENCES

In this example, the respiratory rate is set to 15 breaths per minute. That means the patient will receive a breath every four seconds, regardless if the patient needs a breath.

VENTILATOR ASSISTED PATIENT BREATHING PATTERN

Even if the patient attempts a breath in between the timed breaths, the ventilator will take over and deliver the same volume of air as the timed breath.

Oxygen supplement requirement through Ventilator

(9)     Oxygen saturation (SpO2) is the fraction of oxygen-saturated haemoglobin relative to total haemoglobin in the blood. The human body requires and regulates a very precise and specific balance of oxygen in the blood. Normal arterial blood oxygen saturation levels in humans are 95–100 percent.

 Give oxygen therapy to patients with respiratory failures (i.e. SpO2 < 90%) Initiate oxygen therapy at 5 L/min and titrate to SpO2 ≥ 90% in non-pregnant adults and SpO2 ≥ 92–95 % in pregnant patients.

 Respiratory failure may not be treated by oxygen alone

(10) Fraction of Inspired Oxygen (FiO2) is the concentration of oxygen that a person inhales. The atmospheric air that we inhale on a day to day basis is made up of 21% oxygen (i.e 0.21). Even when high oxygen flows (10 to 15 L/min), delivered through a face mask with reservoir bag, and the concentration of oxygen (FiO2) is high (between 0.60 and 0.95); patients may continue to have increased work of breathing or hypoxemia because of requirement of high mechanical ventilation. There are higher flow oxygen system ventilators that now deliver up to 50–60 L/min flow rates using newer nasal cannula interfaces, which may be required to cure the respiratory failure.

How plentiful is 4-bar oxygen supply

? Absolute minimum oxygen requirement is the human consumption of about 250 ml/min. However, achieving this is only possible if certain breathing system designs are used and ‘driving’ gas is done by air. Specifically, would have to use circle breathing system with active CO2 absorption.

? If consumption in the range 1 to 2 l/min is acceptable, then a wider range of designs is possible, but some very basic designs are not.

? If consumption in the range 10l/min is acceptable, then any possible design can be considered. Considerations - What is the resistance of HMEF-bacterial-viral filters that are to be used with the ventilator? Is it clinically relevant? Is there any need to consider running from only low pressure oxygen, for example, from a concentrator? This makes design more complex. How plentiful is the supply of syringe drivers and drugs for sedation?

? If limited, then a vaporiser could be used to vaporise Isoflurane for sedation, This would need certain breathing system designs, mandatory AGSS and a supply of vaporisers.

? If monitoring can be done by another machine, it could be left out of the ventilator, but essential parameters must be available to the clinician.

Positive Air Pressure Ventilator and its Construction:

Ventilation is the only known available treatment for sufferers of COVID-19. Existing ventilation machines in hospitals are complex general purpose machines costing very high. The availability of the existing ventilators is nowhere near enough to meet the predicted required numbers. Critically ill patients left without ventilation treatment are in danger of losing their life.

PATIENT CIRCUIT WITH VENTILATOR (21)

One effect of the virus as well as damaging the lungs, it also produces a very sticky mucus in the lungs which causes the lungs to collapse and makes it very difficult for the patient to breath of their own accord. Ventilation can be delivered either via intubation or a well sealed mask and delivers continuous positive air pressure into the lungs to keep them inflated at all times. Conscious less ill patents can be aided using a CPAP (Continuous Positive Airway Pressure) ventilation device like a sleep apnea device, this delivers a constant air of the same flow rate and pressure. The more critically ill patients need a machine to breath for them which varies the pressure and flow according to inhale and exhale and relies on maintaining a good seal and a PEEP valve to keep the lungs continually inflated.

CONSTRUCTION OF BAG VALVE MASK (22)

An analogy: Imagine inflating a balloon, letting it deflate completely, then re- inflating it, that is like CPAP. If you inflated the balloon, deflated it half way, then re- inflated it, that's more like the treatment needed for the worse sufferers.

This is an automated bag valve mask (BVM) device utilising off-the-shelf components to provide safe and continuous mechanical ventilation for COVID-19 patients.

This ventilator is a controllable, automated add-on solution to the existing and widely available Bag Valve Mask. The device compresses the BVM with a mechanical system that is able to provide consistent and accurate ventilation with positive- pressure. This solution exists within the top range of ventilator solutions with an a priori design to produce volume and pressure cycled ventilation that includes positive end-expiratory pressure (PEEP) and enriched oxygen sources.

CAD MODEL CONSTRUCTION (18)

CAD MODEL VIEWS (18)

Solution with a Portable and Cost-Effective Ventilator

 The USP of minimalistic design is how easy and fast it can scale for mass production for the following reasons:

 ? Automated production: The production of each part can be fully automated using 3D Printer and Laser cutting machines with minimum number of spares.

? Simple construction: Very few different components will be needed and no exotic parts will be used, mostly manufactured using 3D Printer.

? Lucid mechanism: It will use a simple mechanism with just an actuating shaft mounted to a motor - no complicated mechanisms to go wrong, just one moving part

? Fast assembly: Complete assembly will be possible in minimum time and less personnel required.

? Adjustable settings: Has full adjustment of breath frequency and pressure/tidal volume and with a small adaption can function within all requirements using a micro-controller.

? Low cost

 Avoiding the principle of conventional positive and negative pressure ventilators that are prevalent in medical facilities and have similar frequencies and tidal volumes to natural respiration. Although these ventilators help patients maintain respiration functionality, but they often cause organ damage due to the large volume of the air injection as -

? Use of positive pressure ventilators usually results in a higher airway pressure of about 30 to 40 cmH2O.

? Larger tidal volume may lead to a higher inspiratory pressure and cause lung injury of patients undergoing treatment.

Therefore, high-frequency ventilator can avoid such injuries during while maintaining the functionality of conventional ventilators.

Advantage of high-frequency over a conventional positive pressure ventilator:

1.      By maintaining regulated inflation of the lung over a specific period, high- frequency ventilators can boost the air exchange volume using lower airway pressure and a smaller tidal volume. The small injection volume can avoid lung injury from the use of ventilators and prevent both inappropriate airway pressure elevation and over inflation of the alveoli.

2.      With a smaller injection volume, thinner tube can be used to replace endotracheal tubes with tracheostomy tubes. Tracheostomy tubes will not only enable patients to speak and to feed orally but also eradicate the use of the balloon in the throat which will significantly reduces the unpleasant condition of treatment.

Ventilators use two types of control mechanisms : Volume based or Pressure based

?  Volume based mechanism is based on controlling the inspiration volume. If the patient’s respiratory resistance (R) is large or compliance (E) is small, under the same tidal volume, the Inspiratory Pressure enlarges and lung injury may occur.

? Pressure based approach controls the Inspiratory Pressure but, under the pressure setting, tidal volume varies according to the conditions of each patient’s lungs. To avoid the risk of triggering lung damage, pressure based mechanism is opted in this design.

Portable and cost-effective model of a High-Frequency Ventilator :

Following the schematic diagram of the proposed ventilator functioning -

1. Ventilator has adjustable mechanical controls for the flow rate, oxygen concentration and mechanical adjustable pressure valve.

2. The main components are the flow control pressure valves, pressure gauge meters, flow meters, check valves, gas chamber, and a PEEP switch solenoid valve.

3. Flow control valves are used to regulate the relative flow of air and oxygen to reach different mixture concentrations. The flow meters measure the air and oxygen flow rates and then derive the concentration of oxygen in the air mixture.

HIGH FREQUENCY VENTILATION SYSTEM

4. Mixed gas flows into the gas chamber to be blended. Following this the main component to generate high-frequency air supply comes into picture. It involves 2 compression bags placed side by side and in between a plank is placed attached to motor that compresses compression bag to displace low tidal volume air and further compresses other compression bag as soon it decompresses the first bag.

5. System comprising 2 compression bags can generate low tidal supply of air with a high frequency rate.

6. Finally, the mixed gas then passes through the solenoid valve to reach the output terminal of the ventilator.

7. In a comparison between the single compression bag ventilator and the proposed ventilator and commercially available machines, the proposed design can perform with good linearity and accuracy in the clinically accepted range of 20% to 100%.

 Material required and expected cost :

Possible Versions of High-Frequency Ventilator :

1.    Portable high frequency ventilator with mechanical valves (as above)

2.    Portable high frequency ventilator with feedback control and electronically automatic adjustable valves

3.    Portable high frequency ventilator with dynamic lung monitoring user interface

Portable high frequency ventilator with feedback control and electronic adjustable valves (Version 2) :

To improve the use of resources in healthcare, there is a clear medical foundation for the utility of electronic and micro-controller based ventilators. For patients in ambulances or non-hospital environments, portable, cost-effective and easy to operate devices may be effective for treatment since using reliable portable ventilators (13) may better support home-care contexts by mitigating the heavy burden on patients and medical services.

 A.  Automatic feedback based valve adjustment

ELECTRONIC VALVE FEEDBACK SYSTEM

1. Air and Oxygen sources can be directly connected to electronic operated valves.

2. Ventilator has adjustable controls for the flow rate, oxygen concentration, pressure, and injection volume using electronic valves and a control interface.

3. Flow valves are used to regulate the relative flow of air and oxygen to reach different mixture concentrations. Here pressure is monitored by flow meters and controlled by adjustable flow control.

4. Flow meters measure the air and oxygen flow rates and then derive the concentration of oxygen in the air mixture.

5. Mixed gas flows into the gas blender to be blended.

6. System shall employ a automatic digital control, modifying the flow rate to the expected value.

7. Mixed gas is then passes through the solenoid valve to reach the output terminal of the ventilator.

 B.  Micro-controller based feedback control technique

FEEDBACK CONTROL SYSTEM

1.      I:E ratio [Inspiration:Expiration (I:E) ratio] affect the gas exchange efficiency of the lungs. The I:E ratio is defined as the ratio of the duration of the inspiratory phase to the duration of the expiratory phase and maintains air pressure > 1 atm in lungs after expiration, Hence saves lungs from collapsing.

2.      Pressure feedback system achieves optimal pressure and output flow by implementing feedback. When the ventilator is initiated, the system compares the set and measured values instantly. If the measured value is smaller than the setting, the system sends feedback information to the flow control valves, raising the output flow.

3.      When the Pressure is insufficient, the system reduces the I:E ratio. In this mechanism, under the same output flow, the pressure can be increased effectively.

4.      If oxygen concentration is insufficient, the system directly regulates the flow control valves, increasing the flow of pure oxygen. A programmed micro- controller adjusts these critical parameters of the ventilator.

 C. Solenoid valve adjustment

1. Ventilator includes a frequency control block composed of an oscillator, microprocessor, digital-to-analog converter (DAC), and comparator.

2. Oscillator / Switchable Capacitor array is used to reach a constant frequency in the range of 1– 4 Hz.

3. By creating a reference voltage with the DAC and comparing the output ramp from an oscillator with the adjustable reference voltage, an adjustable I:E ratio in the range of 10% ~ 70% can be attained.

4. Output ramps are the charging and discharging curves of the switchable capacitor in the oscillator. Hence, used to control PEEP (Positive End Expiratory Pressure) of a ventilator.

GENERAL SPECIFICATIONS OF SOLENOID VALVE OUTPUT

D.Air Delivery Technique

AIR DELIVERY CONTROL SYSTEM

 1.        Power Source: A constant 12 volts is applied from the power supply. A 12 volts Lithium battery is used or a DC adapter can be provided so that the ventilator can be directly operated from the main power supply (220 volts).

2.        Motor Driver: It consists of two H-Bridge circuits and PWM is used to address the speed of the motor. Supply of current is done from a battery of the machine, so the principal concern is to limit to that extend which current is needed to be provided and the capacity building of the chip and the battery.

3.        Micro-Controller: Mode of operation can be triggered automatically in response to the feedback and can control motors of the air delivery technique accordingly.

4.        Air Delivery Technique: It works mainly on two strategies. One strategy functions upon the constant pressure source for continuously delivery of air using a Centrifugal Air Pump. Whereas the second strategy supplies uninterrupted air by compressing an air reservoir using a BVM / Ambu Bag.

High frequency ventilator with dynamic lung monitoring (Version 3):

Use of Dynamic Lung Monitoring (20)

1. Because of different operating concepts and different power sources, switching between different modes can be difficult – for example, between a transport ventilator (used for less duration and as a high frequency ventilator) and ICU ventilator (used for long duration and adaptive frequency ventilation).

2. Monitored data displayed as numbers and curves is difficult to interpret.

3. Assessment of weaning criteria is difficult with conventional monitoring.

 Dynamic Lung Panel can be used to display and monitor data in real-time such as -

1. Tidal Volume: Dynamic Lung will expand and contract to show tidal volume in real time. It moves in synchrony with actual breaths, based on the flow sensor signal. Lung size can be shown relative to the "normal" size for the patient’s ideal body weight.

2. Compliance: Dynamic Lung will show compliance (E) breath by breath relative to “normal” values for the patient’s height. The shape of the lungs changes with compliance.

3. Patient triggering: The muscle in the Dynamic Lung will show patient triggering.

4. Resistance: The bronchial tree in the Dynamic Lung will show resistance (R) breath by breath relative to “normal” values for the patient’s ideal body weight.

Past Generations of a Ventilator

 Ventilators have evolved over the last 40 years through at least five generations -

1. First generation ventilators had relatively primitive electrical or pneumatic control circuits. capable of only one mode of ventilation, had uncalibrated dials and no alarms.

2. Second generation devices used simple analog electronic or fluidic control circuits, offered several modes of ventilation, and provided some basic alarms.

3. Third generation machines are characterised by the use of digital electronics (microprocessors), for both control and operator interface functions.

4. Fourth generation ventilators made full use of computerised operator interfaces (CRT and LCD displays). Software developments allowed integration of waveform monitoring, calculated lung mechanics and extensive system diagnostics.

5. The current, fifth generation mechanical ventilator makes use of the “Virtual Instrument” operator interface design along with more advanced control software allowing for a “Universal Machine” that can ventilate neonatal, paediatric, and adult patients.

Production Requirements and Steps

WORKBENCH AND SETUP

Laser Cutter: Laser Cutting CNC’s will be used to cut Acrylic sheets so that the production of each part is fully automated, with minimum number of parts.

3D Printer: Very few different components are needed for assembly, such parts can be 3D Printed so that no exotic parts are needed (not even a motor coupling).

 Certifications and Standards required from MHRA :

? BS EN 794-3:1998 +A2:2009: Particular requirements for emergency and transport ventilators

? ISO 10651-3:1997: Lung ventilators for medical use – emergency and transport

? BS ISO 80601-2-84:2018: Medical electrical equipment. Part 2 to 84. Particular requirements for basic safety and essential performance of emergency and transport ventilators – especially the parts on ‘patient gas pathway’ safety (very similar to IEC 60601)

? BS ISO 19223:2019: Lung ventilators and related equipment. Vocabulary and semantics

Limitations of a Portable and a Cost-Effective Ventilator

In the American Journal of Respiratory and Critical Care Medicine, researchers in Germany and Italy said their Covid-19 patients were unlike any others with acute respiratory distress. Their lungs are relatively elastic (“compliant”), a sign of health “in sharp contrast to expectations for severe respiratory diseases.” Their low blood oxygen might result from things that ventilators don’t fix. Such patients need “the lowest possible [air pressure] and gentle ventilation,” they said, against increasing the pressure even if blood oxygen levels remain low.

The noninvasive devices “can provide some amount of support for breathing and oxygenation, without needing a ventilator,” said ICU physician and pulmonologist Lakshman Swamy of Boston Medical Center. One problem, though, is that continuous positive airway pressure machines and other positive-pressure machines pose a risk to health care workers, he said. The devices push aerosolised virus particles into the air, where anyone entering the patient’s room can inhale them. The intubation required for mechanical ventilators can also aerosolise virus particles, but the machine is a contained system after that (16).

 Risks in Ventilation :

Mechanical ventilation (12) is often a life-saving intervention, but carries potential complications like,

1.      Airway injury

2.      Alveolar damage

3.      Ventilator associated pneumonia

4.      Other complications include decreased cardiac output and oxygen toxicity

5.      Primary complications that presents in patients mechanically ventilated is Acute Lung Injury (ALI) / Acute Respiratory Distress Syndrome (ARDS). ALI / ARDS are recognised as significant contributors to patient morbidity and mortality.

Future Advancements to a low-cost Ventilator

Machine Learning aspect in Ventilation

1.    Mathematical model that relates pressure, volume, and flow during ventilation is known as the equation of motion for the respiratory system:

Pvent + Pmusis = E×V + R×V

where Pvent is the pressure generated by the ventilator, Pmusis the pressure generated by the ventilatory muscles, E is respiratory system compliance, V is lung volume, R is respiratory system resistance,

2.    Lung protective optimal ventilation can be done by machine learning approach for assessment of respiratory resistance (R) and compliance (E).

3.    A pressure control ventilator can be used to predict R and E values, to gather sensor data for validation of the supervised learning algorithms based on decision tree, decision table, and Support Vector Machine (SVM).

4.    Pressure, volume and flow are variable functions of time, all measured relative to their end expiratory values.

5.    These values are normally: muscle pressure = 0, ventilator pressure = 0, volume = functional residual capacity, flow = 0

6.    During mechanical ventilation, these values are: muscle pressure = 0, ventilator pressure = positive end expiratory pressure (PEEP), volume = end expiratory volume, flow = 0

7.    Compliance (E) and Resistance (R) are constants.

References

 (1) Total number of government hospital beds include Central Government, State Government and Local Government bodies (PHCs are also included in the number of hospitals).

(2) Population figures have been used as of year 2019 : https:// www.worldometers.info/world-population/india-population/

(3)  Yeolekar, M. E., and S. Mehta. “ICU care in India-status and challenges” JOURNAL-ASSOCIATION OF PHYSICIANS OF INDIA 56, no. R (2008): 221

(4) India’s Health Infrastructure Report : https://www.brookings.edu/blog/up-front/ 2020/03/24/is-indias-health-infrastructure-equipped-to-handle-an-epidemic/

(5) BMA’s epidemic handling strategy https://www.theguardian.com/society/2020/ apr/01/ventilators-may-be-taken-from-stable-coronavirus-patients-for-healthier- ones-bma-says

(6) According to Minister of State for Health Ashwini Choubey in Rajya Sabha on July 2, 2019 and Business-Standard Report : https://www.business-standard.com/ article/pti-stories/india-has-one-doctor-for-every-1-457-citizens-govt-119070401127_1.html

(7) Genetic Analysis of SARS-Cov-2 : https://www.livescience.com/coronavirus-not- human-made-in-lab.html

(8) Genetic Enzyme Details : https://en.wikipedia.org/wiki/Angiotensin- converting_enzyme_2

(9)  Shortage of Ventilator : https://www.theguardian.com/world/2020/mar/27/howventilators-work-and-why-they-are-so-important-in-saving-people-with- coronavirus

(10) Oxygen supplement requirement : https://support.withings.com/hc/en-us/articles/201494667-What-does-SpO2-mean-What-is-a-normal-SpO2-level-

(11) https://www.who.int/csr/disease/coronavirus_infections/InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf

(12) Mechanical Ventilation : https://en.wikipedia.org/wiki/Mechanical_ventilation

(13) Portable Ventilators IEEE Xplore Library : https://ieeexplore.ieee.org/abstract/ document/8857805

(14) Global Data Analyst : https://www.nsmedicaldevices.com/analysis/coronavirusventilators-global-demand/ : https://www.imperial.ac.uk/media/imperial-college/ medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf

(15) Covid-19: The race to build coronavirus ventilators : https://www.bbc.com/ future/article/20200401-covid-19-the-race-to-build-coronavirus-ventilators

(16) With ventilators running out, doctors say the machines are overused for COVID-19 : https://www.boston.com/news/health/2020/04/08/with-ventilators- running-out-doctors-say-the-machines-are-overused-for-covid-19

(17) Rapidly manufactured ventilator system specification : https://www.gov.uk/ government/publications/coronavirus-covid-19-ventilator-supply-specification/ rapidly-manufactured-ventilator-system-specification

(18) COVID-19 Rapid Manufacture Ventilator BVM Ambu bag OpenVent-Bristol : https://www.instructables.com/id/COVID-19-Rapid-Manufacture-Ventilator-BVM-Ambubag-/

(19) Action of COVID to lungs : https://www.webmd.com/lung/what-does-covid-do- to-your-lungs#1

(20) Ventilation cockpit monitoring system : https://www.hamilton-medical.com/en_IN/Solutions/Ventilation-Cockpit-user-interface.html

(21) UC San Diego Engineers and Doctors Team Up to Retrofit and Build Ventilators with 3D-Printing : https://ucsdnews.ucsd.edu/feature/uc-san-diego-engineers-and- doctors-team-up-to-retrofit-and-build-ventilators-with-3d-printing

(22) Research Paper on mouth to mouth BVM https://www.researchgate.net/publication/263515741_From_Mouth-to- Mouth_to_Bag-Valve- Mask_Ventilation_Evolution_and_Characteristics_of_Actual_Devices- A_Review_of_the_Literature