Journal of Cellular & Molecular Anesthesia (JCMA)

Review Article

Supplemental Oxygen therapy and Non-Invasive Ventilation in

Corona Virus Disease 2019 (COVID-19)
Soudeh Tabashi1, Alireza Mirkheshti1, Mastaneh Dahi1, Dariush Abtahi1, Maryam Vosoughian1, Shahram
Sayyadi1, Mohamadreza Moshari1, Elham Memary1, Shideh Dabir1, Sohrab Salimi1, Ardeshir Tajbakhsh1*

Abstract 1. Anesthesiology Research Center,

The world has experienced a pandemic due to novel Severe Acute Respiratory Shahid Beheshti University of Medical
Sciences, Tehran, Iran
Disease Corona Virus-2 (SARS-CoV2) since December 2019. The clinical
spectrum of the disease known as Coronavirus Disease 2019 (COVID-19) is
so much wide, starting from an asymptomatic state to paucisymptomatic
clinical presentation, pneumonia, respiratory failure to even death.
Supplemental oxygen therapy is essential in managing COVID-19. Also, there
is sparse evidence regarding use of non-invasive ventilation (NIV) in
pandemics like SARS-CoV-2. This study reviews the currently available
methods for respiratory support in COVID-19 with a discussion about using
these modalieties in the COVID-19 pandemic.

Corresponding Author:
Ardeshir Tajbakhsh, MD. Assistant
Keywords: COVID-19, Oxygen, Respiratory support, Non-Invasive Professor, Department of
Ventilation, Severe Acute Respiratory Disease Corona Virus-2 Anesthesiology, Anesthesiology
Research Center, Shahid Beheshti
University of Medical Sciences;
Please cite this article as: Tabashi S, Mirkheshti A, Dahi M, Abtahi D, Vosoughian M,
Tehran, Iran
Sayyadi S, Moshari M, Memary E, Dabir S, Salimi S, Tajbakhsh A. Supplemental Oxygen
Email: ardeshir_tajbakhsh@sbmu.ac.ir
Therapy and Non-Invasive Ventilation in Corona Virus Disease 2019 (COVID-19). J Cell Mol
Tel/Fax: 0098-21-22432572
Anesth. 2020;5(1):27-31.

Introduction oxygenation or ventilation to reduce respiratory work

and to prevent lung injury. This pivotal role can be
Since December of 2019 an outbreak of novel
achieved by either increasing FiO2 or helping the
Coronavirus disease 2019 (COVID-19) was reported
mechanical respiratory system of the patient to deliver
and WHO declared a pandemic by 11 March 2020. In
more oxygen in to the blood stream (4).
28 march of the same year more than 200 countries,
Adequacy of oxygen delivery (DO2) is essential
territories or areas has been infected with more than
for aerobic metabolism; therefore, “Shock state” is
510,000 confirmed cases (1).
defined by tissue hypoxia. COVID-19 interferes with
The clinical spectrum of this disease could range
uptake of oxygen from inhaled gaseous mixture due to
from asymptomatic, mild upper respiratory tract
alveolar damage with cellular fibromyxoid exudates
infection illness, severe viral pneumonia, respiratory
and interstitial mononuclear inflammatory infiltrates
failure and even death (2). Most of the reported
leading to acute respiratory distress syndrome (ARDS)
mortalities are due to alveolar damage and respiratory
(5). In early stages of ARDS acute oxygen therapy can
failure (3). Therefore, at the end of the clinical
lay an integral role in treatment of tissue hypoxia.
spectrum, COVID-19 patients require respiratory
Therefore, understanding basics of oxygen therapy and
support. Respiratory support aims to maintain adequate
the devices used are essential for treating patients with

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Tabashi et al. Supplemental Oxygen Therapy and Non-Invasive Ventilation in Corona Virus Desease 2019 (COVID-2019)

COVID-19. (10).
Non-invasive ventilation (NIV) refers to Simple (Hudson) Mask: At least 5 liter/min of
delivery of positive pressure in to the airway for flow rate is required in order to overcome rebreathing,
ventilation support, without invasive endotracheal also flow rates more than of 10 liters/min would not be
intubation. NIV has been shown to be effective in acute efficient. The FiO2 provided would be 35% to 60%
respiratory failure while avoiding complications of which also depends on flow rate and minute
endotracheal intubation especially ventilator ventilation. (approximately 4% per liter of O2) (13).
associated pneumonia (6). As NIV is proposed as the Reservoir bag (non-rebreather mask): this
first line treatment in patients with acute respiratory device is a facial mask combined with a reservoir bag
failure, NIV in COVID-19 patients might be beneficial with capacity of 600 to 1000 mL and a one-way valve
(7). Besides, NIV is known as aerosol generating connecting these two. These add-ons enable delivering
procedure, therefore there should be cautions in order higher concentrations of oxygen about 85-90% with
to minimize spread of the virus (8). flow rate of 15 liter/min. The mentioned bag and valve
In this review we have discussed how to is designed so that they could stop rebreathing of
maintain oxygenation and the rational use of devices in expired gas. Flow must be sufficient to keep reservoir
patients requiring higher FiO2 and also we have bag from deflating upon inspiration (13).
discussed the controversies regarding non-invasive
ventilation (NIV). 2) High Flow Oxygen Delivery Devices
Supplemental Oxygen Support: Facial mask with Venturi valve: These devices
The first line therapy of hypoxemic patient like have the benefit of overcoming rebreathing due to high
COVID-19 is administration of supplemental oxygen flow rates provided by Venturi valves operating by
(9). Oxygen therapy is defined by administration of Bernoulli principle of jet gas mixing. They are capable
oxygen at concentrations above room air which is of providing low concentrations of O2 (24-30%). But
20.9% (10). There are numerous devices in order to higher flow rates and wider oxygen jet they can
prescribe oxygen. When using these devices some provide FiO2 as high as 60%. Their oxygen
cautions has to be applied in order to gain maximal concentration do not depend on minute ventilation
efficacy for the patient (11). As shown in a multi- hence it depends on oxygen flow rate which is
center study in Wenzhou, China about 90% of COVID- indicated by each valve and should be followed by the
19 patients required oxygen therapy (12). General manufacturer’s preference (14). The nozzles are color
principle in providing oxygen for patients with coded for desirable concentrations of 24% blue, 28%
COVID-19 is that higher flow may result in risk of white, 35% yellow, 40% red and 60% green (10).
viral aerosolization (8). There are two types of oxygen High Flow Nasal Cannula: These relatively new
delivery devices which deliver either the entire (high systems allow humidification and heating the oxygen
flow) or partial (low flow) ventilator requirements. provided for the patient while delivering variable flow
1) Low Flow Oxygen Delivery Devices rates between 1 to 60 Liter/min. Actual FiO2 delivered
Nasal cannula: FiO2 delivered by nasal cannula by these devices is not stable. It depends on the flow
depends on minute ventilation and oxygen flow rate, rate, respiratory rate, peak inspiratory flow rate and
which would be 1-6 liter/min (FiO2 increases also method of breathing (higher with mouth-open
approximately 4% per liter flow from 24% to 44%). breathing than mouth-closed breathing) (11). Their
This device is simple, comfortable and convenient and FiO2 could range from 24% when using low flows up
prevents rebreathing while allowing talking and eating. to more than 70% with high flow rates. although it has
It may cause local irritation and dermatitis with higher not yet been described any contraindications, but in
flow rates and also as the minute ventilation increases cases NIV is contraindicated you should reconsider its
the FiO2 prescribed would decrease (13). When use (15).
administering oxygen via nasal cannula we should There are limited data regarding use of HFNO
consider that complications like drying of mucosal in pandemics, hence a retrospective cohort study in
membrane, nasal trauma or epistaxis could happen

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Supplemental Oxygen Therapy and Non-Invasive Ventilation in Corona Virus Desease 2019 (COVID-2019) Tabashi et al.

Table 1: Pros and Cons of NIV in COVID19 patients with respiratory failure.

Pros Cons
Non-invasive method Need personnel protection equipment
Effective in non-severe respiratory failure Need airborne isolated room
Low rate of mortality Ineffective in severe respiratory failure
Lower ventilator associated pneumonia (VAP) Barotrauma

Wuhan, China, reported mortality of 28% in first analogous to positive end expiratory pressure (PEEP).
month of outbreak. In that study about 20% of patients Bilevel positive airway pressure (BiPAP): This
receiving HFNO, survived (2, 8). Although early mode delivers two different airway pressures, which
invasive ventilation is proposed in some studies, a are inspiratory (IPAP) and expiratory (EPAP). EPAP
cohort study of Influenza A epidemic showed HFNO is analogous to PEEP on CPAP and IPAP is a higher
decreased invasive mechanical ventilation by 45% (8, pressure which helps to increase inspiratory effort of
16). Clinical data of 60 severe cases gathered in the patient (22). Initial pressure setting for EPAP is 3
Jiangsu, China, concluded that early NIV and HFNO cmH2O and for IPAP is 10 cmH2O. Then it should up
combined with prone ventilation can delay intubation titrate in 10-30 minutes to achieve adequate chest
and improved hypoxia in COID-19 patients (17). expansion, IPAP shouldn’t exceed 30 cmH2O (23).
The risk of aerosol production when using Other new modes of delivery can have been
HFNO depends on duration of use, flow rate, patient proposed not limited to proportional assist ventilation
cooperation and sealing of the interface. A well fitted (PAV), average volume assured pressure support
interface would minimize aerosol generation (18). On (AVAPS) and assist/control modes (24).
the other hand, personal protective equipment (PPE) Contraindications of NIV are facial anomalies, recent
are a critical point when using HFNO (16). Also upper gastrointestinal surgery, nausea and vomiting,
negative pressure ventilation rooms are ideal when airway obstruction, inability to protect airway, life
performing aerosol generating procedure and if not threatening hypoxia, confusion and agitation, patient
applicable normal room with strict door policy should refusal, bowel obstruction, and unstable
be used (8). hemodynamics.
These results are suggesting that if mechanical In a retrospective cohort by Zhou in Wuhan at
ventilation became scarce, using HFNO would be a first month of the outbreak of coronavirus disease 2019
necessity in order to provide adequate oxygenation for among 191 patients, about 30% of patients had
these patients (19). Patient selection in this situation dyspnea described by respiratory rate more than
would be critical. Patients with higher risk factors and 24/min. More than half of them supported with
severe illness, that suggests inevitable mechanical invasive ventilation and less than half of them were
ventilation, would not benefit from HFNO (8). supported by non-invasive ventilation the mortality
rate between these two groups was 92% in NIV
Non-Invasive Ventilation compared with 96% in intubated patients (2). Xiabo
Some devices are designed to help ventilation Yang and colleagues (18) describe 52 patients with
and drive force. They can be either invasive also COVID19 that was admitted in Wuhan, China, 29
known as intubation, or non-invasive ventilation patients needed mechanical ventilation that 76% of
(NIV). NIV divides in to two groups; whom required invasive mechanical ventilation
Continuous positive airway pressure (CPAP), although 24% of whom continue their treatment by
this mode delivers high pressure oxygen by a tight non-invasive mechanical ventilation. Mortality rate
fitting mask, attached to a ventilator, in all the times among intubated group was 86% versus 57% in NIV
during respiration. This cannot ventilate patients, it group. These mortality rate in other study on 29
could keep airways and alveolus open during patients was 79% in intubated patients versus 86% in
ventilation. Its use has been verified in sleep apnea and patients supported by non-invasive ventilation (17).
heart failure. Pressure assigned by this device is Mortality rate was higher in patients with invasive

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Tabashi et al. Supplemental Oxygen Therapy and Non-Invasive Ventilation in Corona Virus Desease 2019 (COVID-2019)

mechanical ventilation. The exact cause of death is usage of non-invasive mechanical ventilation in non-
unclear. Intubated patients might have more severe severe form of respiratory failure in patients with
respiratory symptoms and organ failure but this corona virus. These publications suggest that
difference in several studies might be due to the acceptable interface fitting mask while using NIV has
method of oxygen supply in COVID patients. low risk of transmission and cannot create wide spread
Oxygen therapy is one of the main supportive dispersion (28). The other important point in using this
therapies in critically ill patients because most of them method is that the patients need close monitoring to
suffered from organ failure due to hypoxia. Regardless evaluate if treatment failure would happen or not (26).
of oxygen supply method, early oxygen therapy is Other advantages of NIV versus intubation are higher
recommended in various studies (17). Invasive acceptance of patients and health care providers .In
mechanical ventilation is recommended in some some cases with respiratory failure NIV could decrease
studies. But almost all patients had limited life the rate of intubation and its complications like
expectancy after intubation. therefore, more effort are ventilator associated pneumonia (20, 21). Advantage
required in order to evaluate this concept (25). On the and disadvantage of respiratory support by NIV is
other hand, sometimes supportive therapy by NIV is shown in Table 1.
not a choice because of some inevitable reasons like
when there is lack of ventilator, fear of contamination
and uncertainty about intubation(19, 26).
In some studies, it is not recommended to use Conclusion
non-invasive mechanical ventilation for patients with
COVID-19 (9, 18, 27). The main reasons for their Early oxygen support is advised in every patient
concerns are both evidence in support for their with COVID-19, in order to achieve maximal benefit
beneficial aspects, and also the safety properties of basic principles of oxygen support should be
these devices (8, 16). First of all, there are many implemented. Each patient should be considered
concerns about wide spread dispersion of the virus as unique and the appropriate oxygen support device
it was high in other viruses like Middle East should be selected. HFNO has been shown to be
Respiratory Syndrome (MERS) (26). Regardless of the effective in maintaining oxygenation while it may not
belief that NIV is an aerosol generating procedure, have major impact on clinical outcome. HFNO should
reports show that this method is using all over the be used with caution due to its ability to spread the
world in treatment of COVID-19. There are many virus, therefore PPE, negative pressure ventilation
suggestions about using high level of personal rooms or strict door protocols and avoidance of
protection equipment and standard hospital structures positive pressure ventilation rooms are mandatory.
to make effective negative pressure room during There is concern about viral spread through
treatment with NIV(27) (8). Jonathan Chun-Hei aerosolization by NIV. This concern is questionable as
Cheung et al., insist on doing aerosol generating recent studies did not find any differences between
procedures just in airborne infection isolated room and viral spread of NIV versus coughing in patients
with double glove technique (27). suffering from CVOID-19. Also NIV has been shown
The other disadvantage of non-invasive to reduce VAP and decrease rate of invasive ventilation
ventilation is delayed emergent intubation that may in mild to moderate cases. Therefore, its use is
expose the staffs with not enough person protection recommended in non-severe respiratory failure cases
equipment. Patients with non-invasive ventilation are with appropriate PPE.
also at the risk of large tidal volume and barotrauma
due to high transpulmonary pressure. In patients with Acknowledgment
severe respiratory failure beneficial of oxygen therapy None.
by NIV is still questionable. It seems to be better not to
use NIV for severe respiratory failure (8). On the other Conflicts of Interest
hand, in recent studies there are evidences in beneficial

Journal of Cellular & Molecular Anesthesia (JCMA)

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Supplemental Oxygen Therapy and Non-Invasive Ventilation in Corona Virus Desease 2019 (COVID-2019) Tabashi et al.

The authors declare that there are no conflicts of W, Soccal PM, et al. Oxygen therapy for acutely ill medical patients:
a clinical practice guideline. BMJ. 2018;363:k4169.
interest.
15. Sun YH, Dai B, Peng Y, Tan W, Zhao HW. Factors affecting

References
FiO2 and PEEP during high-flow nasal cannula oxygen therapy: A
bench study. Clin Respir J. 2019;13(12):758-64.
16. Murthy S, Gomersall CD, Fowler RA. Care for Critically Ill
1. WHO. Coronavirus disease (COVID-19) Pandemic 2020 [updated
Patients With COVID-19. JAMA. 2020 Mar 11. doi:
28 March 2020, 01:42 GMT+4:30. Available from:
10.1001/jama.2020.3633. [Epub ahead of print].
https://www.who.int/emergencies/diseases/novel-coronavirus-2019.
17. Ramsay M, Hart N. Current opinions on non-invasive ventilation
2. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and
as a treatment for chronic obstructive pulmonary disease. Curr Opin
risk factors for mortality of adult inpatients with COVID-19 in
Pulm Med. 2013;19(6):626-30.
Wuhan, China: a retrospective cohort study. Lancet. 2020.
18. Namendys-Silva, S. A. Respiratory support for patients with
395(10229):1054-62
COVID-19 infection. Lancet Respir Med. 2020;8(4):e18.
3. Sun Q, Qiu H, Huang M, Yang Y. Lower mortality of COVID-19
19. Xie, J., Tong, Z., Guan, X. et al. Critical care crisis and some
by early recognition and intervention: experience from Jiangsu
recommendations during the COVID-19 epidemic in China. Intensive
Province. Ann Intensive Care. 2020;10(1):33.
Care Med (2020).
4. Becker DE, Rosenberg MB, Phero JC. Essentials of airway
20. Bello G, De Santis P, Antonelli M. Non-invasive ventilation in
management, oxygenation, and ventilation: part 1: basic equipment
cardiogenic pulmonary edema. Ann Transl Med. 2018;6(18):355.
and devices. Anesth Prog. 2014;61(2):78-83.
21. Masip J, Peacock WF, Price S, Cullen L, Martin-Sanchez FJ,
5. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al.
Seferovic P, et al. Indications and practical approach to non-invasive
Pathological findings of COVID-19 associated with acute respiratory
ventilation in acute heart failure. Eur Heart J. 2018;39(1):17-25.
distress syndrome. Lancet Respir Med. 2020;8(4):420-422.
22. Mehta S, Hill NS. Noninvasive ventilation. Am J Respir Crit Care
6. Mehta S, Hill NS. Noninvasive ventilation in acute respiratory
Med. 2001;163(2):540-77.
failure. Respir Care Clin N Am. 1996;2(2):267-92.
23. Addala D, Shrimanker R, Davies M. Non-invasive ventilation:
7. Bello G, De Santis P, Antonelli M. Non-invasive ventilation in
initiation and initial management. Br J Hosp Med (Lond).
cardiogenic pulmonary edema. Ann Transl Med. 2018;6(18):355.
2017;78(9):C140-C144.
8. Cook TM, El-Boghdadly K, McGuire B, McNarry AF, Patel A,
24. Rochwerg B, Brochard L, Elliott MW, Hess D, Hill NS, Nava S,
Higgs A. Consensus guidelines for managing the airway in patients
et al. Official ERS/ATS clinical practice guidelines: noninvasive
with COVID-19: Guidelines from the Difficult Airway Society, the
ventilation for acute respiratory failure. Eur Respir J. 2017;50(2).
Association of Anaesthetists the Intensive Care Society, the Faculty
25. Deng Y, Liu W, Liu K, Fang YY, Shang J, Zhou L, et al. Clinical
of Intensive Care Medicine and the Royal College of Anaesthetists.
characteristics of fatal and recovered cases of coronavirus disease
Anaesthesia. 2020 Mar 27. doi: 10.1111/anae.15054.
2019 (COVID-19) in Wuhan, China: a retrospective study. Chin Med
9. Greenland JR, Michelow MD, Wang L, London MJ. COVID-19
J (Engl). 2020.
Infection: Implications for Perioperative and Critical Care Physicians.
26. Chan KW, Wong VT, Tang SCW. COVID-19: An Update on the
Anesthesiology. 2020. [Epub ahead of print]
Epidemiological, Clinical, Preventive and Therapeutic Evidence and
10. Singh V, Gupta P, Khatana S, Bhagol A. Supplemental oxygen
Guidelines of Integrative Chinese-Western Medicine for the
therapy: Important considerations in oral and maxillofacial surgery.
Management of 2019 Novel Coronavirus Disease. Am J Chin Med.
Natl J Maxillofac Surg. 2011;2(1):10-4.
2020:1-26.
11. Nishimura M. High-flow nasal cannula oxygen therapy in adults.
27. Cheung JC, Ho LT, Cheng JV, Cham EYK, Lam KN. Staff safety
J Intensive Care. 2015 31;3(1):15.
during emergency airway management for COVID-19 in Hong Kong.
12. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical
Lancet Respir Med. 2020;8(4):e19.
Characteristics of Coronavirus Disease 2019 in China. N Engl J Med.
28. Cascella M, Rajnik M, Cuomo A, C. DS, Di Napoli R. Features,
2020.
Evaluation and Treatment Coronavirus (COVID-19). In: StatPearls
13. Bateman NT, Leach RM. ABC of oxygen. Acute oxygen therapy.
[Internet] Treasure Island (FL): StatPearls Publishing; 2020 Jan-
BMJ. 1998;317(7161):798-801.
2020.
14. Siemieniuk RAC, Chu DK, Kim LH, Guell-Rous MR, Alhazzani

Vol 5, No 1, Winter 2020

31