Intubated BiPAP Use to Delay Mechanical Ventilation in COVID-19

Guideline · Apr 2020 · 11 min read

In brief

Clinical approach using bilevel positive airway pressure (BiPAP) in intubated COVID-19 patients as a bridge strategy to defer or avoid invasive mechanical ventilation, potentially reducing ventilator-associated complications.

Written by the GCMD Library team from the guideline.

Summary and Background

The COVID-19 pandemic has created an anticipated critical shortage of mechanical ventilators in the United States and globally. With estimates of 160 million potential US infections and only approximately 161,000 ventilators available nationwide, alternative ventilation strategies are urgently needed. This guideline proposes emergency use of bi-level positive airway pressure (BiPAP) devices in intubated COVID-19 patients with ARDS as a bridge therapy to delay or obviate the need for conventional mechanical ventilation.

Need for Ventilators in COVID-19

An estimated 1-3% of COVID-19 infected patients will develop Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation, defined by Berlin Criteria as bilateral infiltrates, normal cardiac function, and PaO2/FiO2 ratio <200. Management goals include maintaining PaO2 >55 mmHg, oxygen saturation >88%, and pH >7.25, with low tidal volume strategy (6cc/kg ideal weight) being the only proven survival-improving treatment. The severity of ARDS is stratified by PaO2/FiO2 ratio while receiving 5 cmH2O CPAP: mild (200-300), moderate (100-200), and severe (<100).

Non-invasive Ventilation as Emergency Alternative

Non-invasive ventilators (NIV) have re-emerged as a management option for hypoxic respiratory failure due to ventilator shortages, increased morbidity from prolonged mechanical ventilation, and barotrauma risks. Recent trials demonstrate that NIV use after intubation does not increase morbidity or mortality compared to high-flow nasal cannula or standard oxygen therapy. Evidence from resource-limited settings shows NIV is 8.75 times less expensive than conventional ventilation with no increased mortality, making continued NIV use after intubation a feasible option when standard ventilators are unavailable.

BiPAP Use in Intubated Patients

Average Volume Assured Pressure Support (AVAPS) mode on newer BiPAP devices allows setting of tidal volume, respiratory rate, EPAP level, and high oxygen concentration, making it suitable for respiratory failure management. Limited literature, including a 2019 Chinese study during early COVID-19, demonstrates that endotracheal intubation with AVAPS ventilation improves dyspnea and gas exchange while reducing positive pressure ventilation adverse events. BiPAP via endotracheal tube has shown improved gas exchange in responders, decreased work of breathing, shorter ventilation duration, improved mental status, and lower cost of care.

AVAPS Initial Settings Protocol

For Smart BiPAP devices with AVAPS capability, initial settings should include Pmin 10, Pmax 20, EPAP 5-10, FiO2 100%, goal minute ventilation 8-15 L/min, and tidal volume 4-6 cc/kg ideal body weight. Arterial blood gas should be obtained at 30 minutes with adjustments based on pH and oxygenation: if oxygen saturation <90%, adjust EPAP as necessary; if pH not >7.25, adjust Pmax. The AVAPS algorithm automatically adjusts pressure support to achieve desired tidal volume, with Pmax set close to mean airway pressure and EPAP adjusted to maintain saturation >90% or FiO2 titrated to maintain PaO2 >60.

Standard BiPAP Settings Protocol

For standard BiPAP devices without AVAPS, begin with IPAP 8, EPAP 4, and FiO2 100%, then assess minute ventilation and rapid shallow breathing index (RSBI <105). Titrate IPAP to achieve tidal volume of 4-6 cc/kg ideal body weight and titrate EPAP to patient comfort or to maintain oxygen saturation >90%. Obtain arterial blood gas at 30 minutes and adjust based on pH and oxygenation parameters, with same escalation criteria as AVAPS protocol.

Minimizing Aerosolization Risk

Previous SARS experience demonstrates BiPAP can be used with coronavirus without excessive healthcare worker risk when appropriate precautions are taken. While BiPAP mask adjustment may be associated with aerosol generation (OR 6.2), this risk is not significantly different from mechanical ventilation. CDC guidance recommends HEPA filtration on ventilator equipment, use of exhalation ports with round-the-tube airflow rather than jets, placement of viral-bacterial filters between mask and exhalation port, and negative-pressure environments when possible.

FDA Emergency Use Authorization

The FDA has issued guidance that for the duration of the public health emergency, it does not intend to object to modifications of FDA-cleared indications for ventilatory devices without prior premarket notification where modifications will not create undue risk. This specifically includes use of sleep apnea devices (CPAP/BiPAP) to treat patients with respiratory insufficiency, provided appropriate design mitigations are in place to minimize aerosolization. Healthcare facilities should prioritize FDA-cleared conventional ventilators when available but may use alternative devices when conventional ventilators are unavailable.

Conclusion and Implementation

While no formal ERS/ATS recommendation exists for NIV in viral pandemic-related acute respiratory failure, available evidence suggests AVAPS via endotracheal tube can serve as a bridge until conventional ventilators become available during the COVID-19 crisis. Immediate physician education is critical, as 48% of acute care hospitals lack intensivists, meaning non-ICU-trained physicians will manage critically ill patients. Proactive training on appropriate BiPAP/AVAPS use, patient selection, device allocation, and titration protocols is essential to prevent poor outcomes related to ventilator shortages.

Statements in this guideline

An estimated 1-3% of those infected by COVID-19 will develop Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation.
ResearchNeed for Ventilators for COVID-19
The Berlin Criteria define ARDS based on radiographic bilateral infiltrates, normal heart function, and a partial pressure of arterial oxygen over oxygen concentration ratio (PaO2/FiO2) of less than 200.
EstablishedNeed for Ventilators for COVID-19
Maintaining oxygen PaO2 above 55 mmHg, oxygen saturations better than 88%, and blood pH above 7.25 is defined within the management of ARDS.
GuidelineNeed for Ventilators for COVID-19
ARDS severity is based on the PaO2/FiO2 ratio while the patient receives 5 cmH2O of continuous positive airway pressure (CPAP), with mild ARDS defined as a ratio of 200-300, moderate 100-200, and severe less than 100.
EstablishedNeed for Ventilators for COVID-19
The only treatment found to improve survival in ARDS is a low tidal volume strategy on ventilator support (6cc/kg ideal weight).
ResearchNeed for Ventilators for COVID-19
A recent trial demonstrated that the use of NIV devices, after intubation, has not led to increased morbidity or mortality when compared to HFNC and standard noninvasive management strategies.
ResearchNon-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions
NIV is 8.75 times less expensive an intervention with no increased mortality associated with use.
ResearchNon-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions
A helmet interface would be preferable to a face mask to minimize air leak, improve outcomes, and provide support for patients in need of positive pressure ventilations.
RecommendationNon-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions
For Average Volume Assured Pressure Support (AVAPS), initial settings should be Pmin 10, Pmax 20, EPAP 5-10, FiO2 100%, Goal Min Vent 8-15 liters/minute, and Tidal Volume 4-6cc/kg.
RecommendationNon-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions
If oxygen saturations are less than 90%, adjust EPAP as necessary.
RecommendationNon-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions
If pH is not over 7.25, adjustment of Pmax will likely be needed.
RecommendationNon-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions
Obtain an ABG at 30 minutes and make adjustment as necessary based on pH levels or oxygen.
RecommendationNon-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions
For standard BiPAP, begin with settings of IPAP 8, EPAP 4, and FiO2 100%.
RecommendationNon-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions
Titrate IPAP to Tidal Volume of 4-6 cc/kg.
RecommendationNon-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions
Titrate EPAP that is comfortable or maintains oxygen saturations greater than 90%.
RecommendationNon-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions
Endotracheal intubation with AVAPS ventilation improved dyspnea and gas exchange and reduced relative adverse events caused by positive pressure ventilation.
ResearchUse of BiPAP in Intubated Patients
BiPAP with endotracheal tube connected via T-tube demonstrated improved gas exchange in responders, decreased work of breathing, lower ventilation days, and improved mental status (GCS score ≥8) with the added benefit of lower cost of care.
ResearchUse of BiPAP in Intubated Patients
Non-invasive ventilation (NIV) has been reported to be efficacious in the treatment of SARS-related ARF without posing infection risks to healthcare workers.
ResearchEmergency Use While Minimizing Aerosolization
BiPAP mask adjustment may be associated with aerosol generation risk (odds ratio 6.2, 95% confidence interval 2.2-18.1), but this risk is not significantly different from that of mechanical ventilation.
ResearchEmergency Use While Minimizing Aerosolization
BVMs and other ventilator equipment should be equipped with HEPA filtration to filter expired air.
RecommendationEmergency Use While Minimizing Aerosolization
EMS organizations should consult their ventilator equipment manufacturer to confirm appropriate filtration capability and the effect of filtration on positive-pressure ventilation.
RecommendationEmergency Use While Minimizing Aerosolization
Healthcare facilities should use FDA-cleared conventional/standard full-featured ventilators to treat patients who develop respiratory failure or respiratory insufficiency wherever possible.
RecommendationEmergency Use While Minimizing Aerosolization
Recommended measures to reduce risk include the use of exhalation ports with round-the-tube airflow rather than jets, placement of a viral-bacterial filter between the mask and the exhalation port, and a negative-pressure environment.
RecommendationEmergency Use While Minimizing Aerosolization
To date, no ERS/ATS recommendation has been made (positively or negatively) for NIV in either de novo ARF or ARF in a viral pandemic.
OpenConclusion

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© 2020 Syneos Health®. All rights reserved. Intubated BiPAP Use to Delay Mechanical Ventilation in COVID-19 March 2020 Keith Robinson, MD, MS, FCCP; Peter Polos, MD, PhD, FCCP, FAASM; Jeffrey J. Stewart, MA.

INTUBATED BIPAP USE TO DELAY MECHANICAL VENTILATION IN COVID-19 2 | © 2020 Syneos Health®. All rights reserved. Table of Contents Summary ...................................................................................................................................................3 Background ...............................................................................................................................................3 Need for Ventilators for COVID-19 ......................................................................................................... 4 Non-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions ........................................................................4 Use of BiPAP in Intubated Patients ......................................................................................................... 7 Emergency Use While Minimizing Aerosolization ................................................................................8 Conclusion .................................................................................................................................................9 References ...............................................................................................................................................10

Background The world is currently experiencing the 2019-nCOV (COVID-19) pandemic. There are no vaccines or approved treatments for this virus, which infects its host, causes pneumonia, and leads to acute hypoxic respiratory failure. As COVID-19 spreads around the world, it is likely the availability of mechanical ventilators will be insufficient to meet the needs of the general population (WHO 2020). Some estimates by the CDC predict that 160 million in the US could be infected during the current pandemic, resulting in 2.4 million hospitalizations (CDC COVID-19 Response Team 2020). At last estimate, there are only 62,000 full-featured ventilators and approximately 99,000 older ventilators in hospitals nationwide (Centers for Disease Control 2020) (Ramsey 2020). INTUBATED BIPAP USE TO DELAY MECHANICAL VENTILATION IN COVID-19 3 | © 2020 Syneos Health®. All rights reserved. Summary A critical shortage of mechanical ventilators is anticipated in many countries, including the United States, because of the ongoing COVID-19 pandemic. A potential emergency solution would be the use of bi-level positive airway pressure (BiPAP). BiPAP may be used in the hospital setting with appropriate precautions for intubated COVID-19 patients experiencing Acute Respiratory Distress Syndrome (ARDS). Use of BiPAP on an emergency basis may delay or obviate the need for mechanical ventilation in appropriate COVID-19 patients.

Need for Ventilators for COVID-19 An estimated 1-3% of those infected by COVID-19 will develop Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation. ARDS is a lung condition that results in hypoxic respiratory failure and can be mild, requiring only increased oxygen concentration via nasal cannula, to severe, necessitating oral tracheal intubation with mechanical ventilation. The Berlin Criteria define ARDS based on radiographic bilateral infiltrates, normal heart function, and a partial pressure of arterial oxygen over oxygen concentration ratio (PaO2/FiO2) of less than 200 (Fan, et al. 2017). Defined within the management of ARDS is maintaining oxygen PaO2 above 55 mmHg, oxygen saturations better than 88%, and blood pH above 7.25 (Fan, et al. 2017). ARDS severity is based on the PaO2/FiO2 ratio while the patient receives 5 cmH2O of continuous positive airway pressure (CPAP) (Fan, et al. 2017). Mild ARDS is a ratio of 200-300, moderate 100-200, and severe <100. Most patients with ARDS are placed on a mechanical ventilator when any of these parameters cannot be maintained with supplemental oxygen delivery or if the work of breathing index is high, placing the patient at risk of respiratory fatigue and failure. The only treatment found to improve survival in ARDS is a low tidal volume strategy on ventilator support (6cc/kg ideal weight) (Ramsey 2020) (WHO 2020) (Patel, Wolfe and Pohlman 2016). Non-invasive Ventilators to Delay Use of Standard Mechanical Ventilators Under Emergency Conditions The dearth of mechanical ventilators (Ramsey 2020), the increased morbidity associated with prolonged mechanical ventilation, and barotrauma to the airways of the lung have ushered in the return of non-invasive ventilators (NIV) as part of management in hypoxic respiratory failure (Siegel and Hyzy 2019). A recent trial comparing standard oxygen therapy, high-flow nasal cannula, and NIV demonstrated that the use of NIV devices, after intubation, has not lead to increased morbidity or mortality when compared to HFNC and standard noninvasive management strategies (Akhter and Rizvi 2017). Lessons learned from developing countries with limited ICU resources conclude NIV is 8.75 times less expensive an intervention with no increased mortality associated with use (Rawat, et al. 2012) (Akhter and Rizvi 2017). While NIV via a face mask or helmet interface is recognized as a bridge supportive mode in ARDS, using an endotracheal tube has not been evaluated in COVID-19 subjects and, as such, is the clinical call of the physician. We suggest continued NIV use, after intubation, may be feasible due to worsening respiratory status and provides a means to ventilate/oxygenate patients until a standard ventilator becomes available or in lieu of a standard ventilator if all are in use. Hospitals and clinicians should continue best practices locally when undergoing NIV with intubation. A helmet interface would be preferable to a face mask to minimize air leak, improve outcomes, and provide support for patients in need of positive pressure ventilations. See algorithm (Figure 1). INTUBATED BIPAP USE TO DELAY MECHANICAL VENTILATION IN COVID-19 4 | © 2020 Syneos Health®. All rights reserved.

INTUBATED BIPAP USE TO DELAY MECHANICAL VENTILATION IN COVID-19 5 | © 2020 Syneos Health®. All rights reserved. Figure 1 Continued on next page For Smart BiPAP If O2 saturations are less than 90%, then adjust EPAP as necessary If pH is not over 7.25, then will likely need adjustment of Pmax Intubate Average Volume Assured Pressure Support (AVAPS) Initial Settings 3 settings to check ABG 30 minutes, make adjustment as necessary based on pH levels or O2 Pmin: 10 Pmax: 20 EPAP: 5-10 1. Choose Pmax setting close to the Mean Airway Pressure that the machine is giving back 2. AVAPS mode will adjust Pressure Support to desired Tidal Volume 3. May need to change EPAP to: • >10 to achieve saturation over 90% or • adjust FiO2 to maintain PaO2 >60 FiO2: 100% Goal Min Vent: 8-15 liters/minute Tidal Volume: 4-6cc/kg

INTUBATED BIPAP USE TO DELAY MECHANICAL VENTILATION IN COVID-19 6 | © 2020 Syneos Health®. All rights reserved. Figure 1, continued For Standard BiPAP If O2 saturations are less than 90%, then adjust EPAP as necessary If pH is not over 7.25, then will likely need adjustment of Pmax Intubate Standard BiPAP Begin With Settings Assess ABG 30 minutes, make adjustment as necessary based on pH levels or O2 IPAP: 8 EPAP: 4 FiO2: 100% • Minute Ventilation • RSBI <105 Titrate IPAP to Tidal Volume: 4-6 cc/kg Titrate EPAP that’s comfortable or maintains O2 saturations >90%

Use of BiPAP in Intubated Patients Average Volume Assured Pressure Support (AVAPS) is an algorithm-based BiPAP mode found on newer standard NIV devices used in the hospital setting. The ability to set a tidal volume (average), respiratory rate, expiratory positive airway pressure level, and higher concentration of oxygen provided makes AVAPS plausible in patients with respiratory failure (WHO 2020). Further, AVAPS use in disease states with poor lung compliance, similar to ARDS, is an added benefit of the algorithm. There is limited literature on its use with oral tracheal intubated patients. Recently, at the CHEST International Convention 2019, an abstract from China— during the onset of COVID-19—found endotracheal intubation with AVAPS ventilation improved dyspnea and gas exchange and reduced relative adverse events caused by positive pressure ventilation (Han, et al. 2019). In another landmark paper, BiPAP with endotracheal tube connected via T-tube also demonstrated improved gas exchange in responders, decreased work of breathing, lower ventilation days, and improved mental status (GCS score ≥8) with the added benefit of lower cost of care (Akhter and Rizvi 2017). INTUBATED BIPAP USE TO DELAY MECHANICAL VENTILATION IN COVID-19 7 | © 2020 Syneos Health®. All rights reserved.

INTUBATED BIPAP USE TO DELAY MECHANICAL VENTILATION IN COVID-19 8 | © 2020 Syneos Health®. All rights reserved. Emergency Use While Minimizing Aerosolization Previous experience with SARS has shown that BiPAP with a coronavirus may be used without excessive risk to the healthcare provider in an emergency setting. “Despite concern about potential aerosol generation, non-invasive ventilation (NIV) has been reported to be efficacious in the treatment of SARS-related ARF without posing infection risks to healthcare workers” (Yam, Chen and Zhong 2003). In small-sample-size studies with ARDS, BiPAP mask adjustment may be associated with aerosol generation risk (odds ratio 6.2, 95% confidence interval 2.2-18.1) as is NIV (study 1 OR 2.6, 95% CI 0.2-34.5; study 2 OR 3.2, 95% CI 1.4-7.2); however, this risk is not significantly different from that of mechanical ventilation (Tran, et al. 2012). Nonetheless, COVID-19 aerosol formation during BiPAP should be minimized and managed in the emergency setting to the extent practical. The CDC has provided guidance for the potential precautions to use for BiPAP for COVID-19 patients. “EMS clinicians should exercise caution if an aerosol-generating procedure (e.g., bag valve mask (BVM) ventilation, oropharyngeal suctioning, endotracheal intubation, nebulizer treatment, continuous positive airway pressure (CPAP), bi-phasic positive airway pressure (BiPAP), or resuscitation involving emergency intubation or cardiopulmonary resuscitation (CPR) is necessary. • BVMs, and other ventilator equipment, should be equipped with HEPA filtration to filter expired air. • EMS organizations should consult their ventilator equipment manufacturer to confirm appropriate filtration capability and the effect of filtration on positive-pressure ventilation.” (CDC 2020) The US FDA has released guidance that reads “…wherever possible, healthcare facilities should use FDA-cleared conventional/standard full-featured ventilators to treat patients who develop respiratory failure or respiratory insufficiency. However, for the duration of the public health emergency, to help foster the wider availability of devices for patients in need of ventilatory support, FDA does not intend to object to modifications to the FDA-cleared indications, claims, or functionality of these devices, without prior submission of a premarket notification where the modification will not create an undue risk in light of the public health emergency. Examples of circumstances where FDA currently believes a modification would not create such undue risk include: … The use of devices indicated for sleep apnea (including noncontinuous ventilators delivering continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) to treat patients with respiratory insufficiency, provided that appropriate design mitigations are in place to minimize aerosolization” (FDA 2020). Additional recommended measures to reduce risk include the use of exhalation ports with round-the-tube airflow rather than jets, placement of a viral-bacterial filter between the mask and the exhalation port, and a negative-pressure environment (Yam, Chen and Zhong 2003).

INTUBATED BIPAP USE TO DELAY MECHANICAL VENTILATION IN COVID-19 9 | © 2020 Syneos Health®. All rights reserved. Conclusion To date, no ERS/ATS recommendation has been made (positively or negatively) for NIV in either de novo ARF or ARF in a viral pandemic (Rochwerg, et al. 2017). Nonetheless, COVID-19 appears to be an extraordinary event that may stress limited ventilator resources such that they may be unavailable for some ARDS patients. Although a full evidentiary package is not available, what evidence we have suggests AVAPS via endotracheal tube, in the right setting, can work as a bridge of support until a conventional ventilator becomes available. Physician education will be needed in the immediate term to inform of appropriate BiPAP procedures in COVID-19. Nearly half (48%) of acute care hospitals have no intensivists, which implies doctors without ICU training will be left to care for the critically ill. Proactive education of these clinicians to the benefit of BiPAP/AVAPS, up to and/or after intubation, will be needed to prevent poor outcomes related to lack of an adequate number of ventilators. Further, any off-label use of a device by this physician population will require training to ensure the correct patient selection, device allocation, and BiPAP titration (CDC COVID-19 Response Team 2020). Note: Syneos Health is coordinating with BiPAP manufacturers to prepare training materials in multiple media to be available for healthcare providers at COVID-BiPAPinfo.com. Although a full evidentiary package is not available, what evidence we have suggests AVAPS via endotracheal tube, in the right setting, can work as a bridge of support until a conventional ventilator becomes available.

INTUBATED BIPAP USE TO DELAY MECHANICAL VENTILATION IN COVID-19 10 | © 2020 Syneos Health®. All rights reserved. References 1. Akhter, Nousheen, and Nadeem Ahmed Rizvi. 2017. “Application of BiPAP through Endotracheal Tube in Comatose Patients with COPD Exacerbation.” Pakistan Journal of Medical Science 33 (6): 1444-1448. 2. CDC COVID-19 Response Team. 2020. Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020. MMWR. Accessed March 20, 2020. doi:10.15585/mmwr.mm6912e2. 3. CDC. 2020. “Interim Guidance for Emergency Medical Services (EMS) Systems and 911 Public Safety Answering Points (PSAPs) for COVID-19 in the United States.” www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-for-ems.html. 4. CDC. March 18, 2020. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/summary.html. 5. Fan, Eddy, Lorenzo Del Sorbo, Ewan Goligher, and et al. 2017. “An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome.” Am J Respir Crit Care Med 195 (9): 1253-1263. doi:10.1164/rccm.201703-0548ST. 6. FDA. 2020. “Enforcement Policy for Ventilators and Accessories and Other Respiratory Devices During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency.” www.fda.gov/regulatory-information/search-fda-guidance-documents/ enforcement-policy-ventilators-and-accessories-and-other-respiratory-devices-during-coronavirus. 7. Han, Boxue, Lei Sun, Guifeng Zhao, Guoru Yang, Maoliang Tian, Lili Dong, Dongxia Wang, and Suiyang Zhang. 2019. “Advanced Device with Auto-titrating EPAP for ARDS Patients.” Chest J 156 (4): A996. doi:10.1016/j.chest.2019.08.921. 8. Patel, BK, KS Wolfe, and AS Pohlman. 2016. “Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome.” JAMA 315 (22): 2435-2441. 9. Ramsey, Lydia. 2020. Business Insider. March 6. https://www.businessinsider.com/presentation-us-hospitals-preparing-for- millions-of-hospitalizations-2020-3. 10. Rawat, Jagdish, Girish Sindhwani, Debasis Biswas, and Ruchi Dua. 2012. “Role of BiPAP applied through endotracheal tube in unconscious patients suffering from acute exacerbation of COPD: a pilot study.” Int J Chron Obstruct Pulmon Dis 7: 321-325. doi:10.2147/COPD.S30126. 11. Rochwerg, Bram, Laurent Brochard, Mark Elliott, and et al. 2017. “Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure.” Eur Respir J 50 (1602426): 1-20. doi:10.1183/13993003.02426-2016. 12. Siegel, Mark D, and Robert C Hyzy. 2019. “Ventilator management strategies for adults with acute respiratory distress.” UpToDate. November 26. Accessed March 22, 2020. www.uptodate.com/contents/ventilator-management-strategies-for- adults-with-acute-respiratory-distress-syndrome. 13. Tran, Khai, Karen Cimon, Melissa Severn, Carmen Pessoa-Silva, and John Conly. 2012. “Aerosol Generating Procedures and Risk of Transmission of Acute Respiratory Infections to Healthcare Workers: A Systematic Review.” PLOS ONE. doi:10.1371/ journal.pone.0035797. 14. WHO. 2020. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. WHO REFERENCE NUMBER: WHO/2019-nCoV/clinical/2020.4. https://www.who.int/publications-detail/clinical-management- of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected. 15. Yam, Loretta, Rong Chen, and Nan Zhong. 2003. “SARS: ventilatory and intensive care.” Respirology 8: S31-S35.

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