Respiratory Support For Adult Patients With Covid

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Respiratory Support for Adult Patients with Covid-19

Jessica S. Whittle MD PhD1 , Ivan Pavlov MD2 , Alfred D. Sacchetti MD3,4, Charles Atwood

MD5,6 , Mark S. Rosenberg DO, MBA7

1Department of Emergency Medicine, University of Tennessee/ Erlanger Health, Chattanooga,

Tennessee, USA

2Department of Emergency Medicine, VerdunHospital, Montreal,Quebec, Canada

Our Lady of LourdesMedical Center, Camden, New Jersey, USA


3

Thomas Jefferson University, Philadelphia,Pennsylvania, USA


4

5University of Pittsburgh and UPM, Pittsburgh, Pennsylvania, USA

6 Department of Sleep Medicine, Pittsburgh Healthcare System, Pittsburgh,Pennsylvania,USA

St. Joseph Healthcare, Paterson, New Jersey, USA


7

Abstract

The COVID-19 pandemic is creating unique strains on the healthcare system. While only a

small percentage of patients require mechanical ventilation and ICU care, the enormous size

of the populations affected means that these critical resources may become limited. A number

of non-invasive options exist to avert mechanical ventilation and ICU admission. This is a

clinical review of these options and their applicability in adult COVID-19 patients. Summary

recommendations include: (1) Avoid nebulized therapies. Consider metered dose inhaler

alternatives. (2) Provide supplemental oxygen following usual treatment principles for

hypoxic respiratory failure. Maintain awareness of the aerosol-generating potential of all

devices, including nasal cannulas, simple face masks, and venturi masks. Use non-rebreather
masks when possible. Be attentive to aerosol generation and the use of personal protective

equipment. (3) High flow nasal oxygen is preferred for patients with higher oxygen support

requirements. Non invasive positive pressure ventilation may be associated with higher risk

of nosocomial

transmission. If used, measures special precautions should be used reduce aerosol formation.

(4) Early intubation/mechanical ventilation may be prudent for patients deemed likely to

progress to critical illness, multiorgan failure, or acute respiratory distress syndrome (ARDS).

KEYWORDS
BiPAP, coronavirus,COVID-19, high flow nasal cannula, high flow oxygen, high velocity

nasal insufflation, non-invasive ventilation, SARS-CoV-2, viral pneumonia

1 INTRODUCTION

A novel clinical syndrome caused by a previously unknown coronavirus, SARS-Cov-2,

was first identified in Wuhan (China) in December 2019. Despite massive efforts to contain

viral transmission, a worldwide epidemic has developed from this virus. This disease is

presently known as COVID-19. The COVID-19 pandemic has several features that are

straining healthcare systems.1,2 The case fatality rate is extremely age dependent with an

increase from <0.6% to 2.2% at age 60 and increasing to over 9.3% at age 80.3 The mode of

spread and transmissibility is via respiratory droplets. The high level of contagion combined

with the lack of immunity to this virus in the population has resulted in an overwhelming

number of severe or critical cases. In Italy, the number of critically illCOVID-19 cases has

exceeded the intensive care unit (ICU) capacity of affected regions, and inNYC, critical

illness fromCOVID-19 has already far exceeded existing ICU capacity. In the US, critical
care capacity was limited even before the COVID-19 pandemic with over one-third of

patients having to wait 6 hours or more for transfer to an ICU.4,5

A number of non-invasive options exist to support COVID-19 patients with mild or

moderate respiratory distress and may reduce the numbers of patients requiring intubation,

mechanical ventilation, and ICU admission in some severely ill patients.19 However, all forms

of supplemental oxygenation and respiratory support may potentially aerosolize respiratory

pathogens.6-8 Selection of respiratory support for patients affected by COVID-19 must

balance the clinical benefit of the intervention against the risks of nosocomial spread.

Complicating this goal is that mitigation of aerosolization by early endotracheal intubation

commits to the prolonged use of an ICU bed and mechanical ventilator, which may not be

available in the context of a pandemic. Therefore, management of the COVID-19-associated

respiratory failure must consider the full spectrum of invasive and non-invasive ventilation

options.

In this clinical review, we summarize the options and provide practical recommendations

for respiratory support in COVID-19 patients.

2 ISOLATION AND PERSONAL PROTECTIVE EQUIPMENT


Any patient suspected of havingCOVID-19 disease should be managed in a negative

pressure room when possible. This is particularly true for patients requiring any form of

supplemental oxygen therapy. Staff treating the patient should use maximum PPEs with N-95

masks and eye protection. When no negative pressure room is available, a closed room may

be the only option. Simple measures such as placing a surgical mask over all patients in the

ED may be helpful in mitigating the pathogenic spread.

3 SUPPLEMENTAL OXYGEN

Oxygen therapy is recommended by the World Health Organization (WHO) and Centers

for Disease Control and Prevention (CDC) as the first-line therapy for treating
COVID-19-induced respiratory distress and hypoxia.2,9 Methods of administration vary and

should be determined by severity of illness. The goal of treatment should be maintenance of

oxygen saturation >90%. The target of treatment should be SaO2 = 92%–95% for pregnant

women.2,10 3.1 Nasal cannula

Supplemental oxygen by nasal cannula provides up to about 5–6 L/min of flow

increasing fraction of inspired oxygen (FiO2) to approximately

FIGURE 1 Aerosol dispersion distances (cm) for various oxygen supplementation

modalities. Distance depicted is the average dispersal for that modality over the range of

flow rates typically used for that modality (NC ranges 3-40 cm, SMat all flows ≈ 30 cm,

VM range 33-40 cm, NRMat all flows < 10 cm, HFNO ranges 4.8-17 cm, NiPPV ranges

85-95 cm, and nebulizers < 80 cm). Note that normal tidal breathing was not measured,

but the distance measured at a flow rate of 1L/min via nasal cannula was 30 cm.

45%. The actual FiO2 may be variable depending on the patient’s inspiratory peak flow.

Limitations of flow in the tubing and entrainment of room air prevent higher effective

oxygen concentrations regardless of the wall settings. Adequate humidification of the


supplemental oxygen is needed to maintain mucociliary action.11,12 While effective for

mildly hypoxic patients, supplemental oxygen delivered by nasal cannula can induce

significant dispersion of exhaled air, even at low flow rates. In studies using a high fidelity

human mannequin model, the reported maximal distance of exhaled air dispersion was 30
cm at 1 L/min, and 40 cm at 5 L/min (Figure 1).12

3.2 Simple mask

Simple masks provide supplemental oxygen with flow rates up to approximately

5–10 L/min. Respiratory rate and exhalation are controlled by the patient and these

individually affect the actual FiO2 delivered. Oxygen supplementation via simple mask is

only marginally greater than that of nasal cannula. High fidelity human mannequin model

studies showed the maximum exhaled dispersion distance using a simple mask at 10

L/minwas 40 cm (Figure1).12

3.3 Venturimask

Supplemental oxygen by venturi mask allows more precise oxygen delivery. FiO2

is delivered in discrete levels, typically between 24% and 60% oxygen. The mask uses an

air/oxygen entrainment device (venturi) to more precisely mix air and oxygen. Each FiO2

level is achieved with a “snap-on” venturi, which specifies the oxygen flow rate to achieve

the selected FiO2. Oxygen flow rates are specified, and typically vary from 2 to 15 L/min.

In studies using a high fidelity human mannequin model, the maximum exhaled dispersion

distance varied from 33 cm at FiO2 40%, to 40 cmat FiO2 24% (Figure 1).12

3.4 Non-rebreather masks

Non-rebreather masks (NRBs) offer a safe way to provide supplemental oxygen to

COVID-19 patients as the mask helps to limit the dispersion of droplets. NRB masks can

provide supplemental oxygen up to a level of approximately 90% at flow rates

approaching 15 L/min.13 To prevent hypercapnia, the reservoir bag must remain inflated at

all times; this requires flow rates of at least 8–10 L/min.14 High fidelity human

mannequin studies demonstrate that the maximum exhaled dispersion distance at 10 L/min

is <10 cm, suggesting that this modality generates the least dispersed aerosols (Figure 1).1
4 INTERMEDIATE THERAPIES

4.1 High flow oxygen systems


High flow nasal oxygen (HFNO) includes high flow nasal cannula and high velocity

nasal insufflation. High flow oxygen systems provide oxygen-rich heated humidified gas to

the patient’s nose at flow levels sufficient to deliver a constant, precisely set high FiO2.

HFNO flow rates reach up to 60 L/min, whereas HVNI delivers flow rates up to 40 L/min

due to differing mechanisms of delivery. Exhalation is to the open air. HFNO reduces dead

space, provides low levels of PEEP, and decreases breathing frequency and work of

breathing.20 The use of HFNO was associated with lower mortality in hypoxemic respiratory

failure.21 Compared to conventional oxygen therapy, HFNO is associated with decreased

risk of subsequent intubation (relative risk [RR] 0.85, 95% confidence interval [CI]

0.74-0.99)22 and need for ICU admission.23,24

Initial concern existed on the risk of aerosolization with HFNO leading some to

recommend avoiding use of this modality. However, the degree of aerosolization has been

shown to minimal with these devices, and it is now recommended as the oxygenation

therapy of choice in patients with respiratory distress. Guidelines from theWHO,2 the Italian

Thoracic Society,15 the Respiratory Care Committee of the Chinese Thoracic Society,16 The

Australian and New Zealand Intensive Care Society,17 and a joint statement from the

German Intensive Care, Anesthesia, and Emergency Medicine Societies, 18 as well as the

joint guidelines produced by the European Society of Intensive Care Medicine and The

Society of Critical Care Medicine,19 all recommend HFNO as a therapy for COVID-19

respiratory failure. Recent publications suggest that newer HFNO and non-invasive positive

pressure ventilation (NIPPV) systems with good interface fitting do not create widespread

dispersion of exhaled air and therefore may be associated with low risk of airborne
transmissions.2,17

Because of their construction, HF/HV systems demonstrate favorable safety profiles as

an AGP. A high-fidelity mannequin study demonstrated that even at the highest setting of

60 L/min, exhaled air dispersion was 17 cm in a healthy lung scenario and only 4.8 cm in a

severely diseased lung scenario.25 The authors cautioned that if the connection from the

tubing to the nasal cannula becomes disconnected there might be a risk of lateral dispersion

of oxygen andpathogens.25 Some guidelines recommend placement of a surgical mask over

patients being treated with high flow therapies as a secondary safety measure.18 High

fidelity human mannequin simulation studies show surgical masks do, in fact, reduce

exhaled air dispersion (Figure 1).26


If HFNO oxygen therapy is used, medical staff should use airborne protection, and the

patient should be treated in a negative pressure room, if available.2,17

There is no currently published evidence that HFNO is a risk factor for nosocomial

transmission of respiratory pathogens.27-30 During the 2003 Toronto SARS-CoV outbreak,

HFNO was not found to be a risk factor for transmission to healthcare workers.29 This is in

contrast with endotracheal intubation, which was strongly associated with transmission to

healthcare workers during the SARS epidemic.29

For the treatment of pneumonia, HFNO was associated with reduced mortality

compared to NIPPV. 21 Additionally, in a small study of severe 2009 influenza A/H1N1v,

20 of 25 patients could not maintainSpO2 >92% with 9 L/min of oxygen administered by

conventiona lnasal cannula. Of those 20 patients, 9 were successfully treated with HFNO

and 11 went on to need mechanical ventilation.30

Given the current circumstances of an overwhelming pandemic, randomized controlled

trials to establish that HFNO reduces the risk of endotracheal intubation (and thus escalation

of care to the ICU) in severe COVID-19 are likely not feasible. However, in a retrospective
study of 610 patients from China, where 10% of the affected patients required critical care,31

a multi-pronged intervention that included early, and aggressive, use of HFNO was

associated with reduced need for mechanical ventilation (<1% vs national average of 2.3%)

and lower mortality (3.33% vs 4.34% in a nearby province).32

There are currently no defined criteria for HFNO failure, but patients who require

vasopressor support30,34 and whose respiratory rate and thoracoabdominal asynchrony are

not rapidly relieved with HFNO35 are potentially at high risk of HFNO failure. Recently, the

“ROX Index” was developed to aid in the prediction of clinical outcomes of patients treated

with HFNO. It is calculated by the ratio of oxygen saturation as measured by pulse oximetry

/FiO2 to respiratory rate. A ROX Index >4.88 is predictive of success, meaning the patient

is unlikely to progress to needing mechanical ventilation.36 Patients with established ARDS

should move rapidly to mechanical ventilation, and treated per published

recommendations.37,38

4.2 Non-invasive positive pressure ventilation

Continuous positive airway pressure (CPAP) or bi-level positive airway pressure

(BiPAP) are respiratory support devices that deliver positive airway pressure through tight

fitting facial or nasal masks. The hallmark of these devices is that they deliver this positive
pressure through all phases of the respiratory cycle. The patient continues to breath

spontaneously both with and against the positive airway pressure. These devices can

provide a FiO2 of up to 100% in a closed circuit.

The risk of aerosol formation and dispersion for CPAP and BiPAP systems are variable

depending on setting parameters and model/mask type. Viral filters can be attached to the

exhalation line on most newer models. High fidelity human model studies demonstrated that

exhaled air dispersed to 40 cm with nasal cannula, and to 64 cm at 10 cmH2O

inspiratory air pressure with a BiPAP mask. That distance increased to 85 cm and >95
cm at 18 cmH2O depending on mask style. This work was performed inside a negative

pressure room (Figure 1).11,12,25 Helmet mask BiPAP is unique and a similar mannequin

study showed that it is safer than other models. The maximal measured dispersal distance

from the helmet-neck interface was 2.7 cm when an air cushion was in place around the

neck (missing air cushions cause severe dispersion).11

The use of CPAP or BiPAP is debated in patients with COVID-19. These modalities

(also called NIV or NIPPV) are included in recommendations by the WHO, 2 the Italian

Thoracic Society,15 and the Respiratory Care Committee of the Chinese Thoracic Society,16

but were not included in a more limited paper by intensive care physicians in France.34 The

Australian and New Zealand Intensive Care Society Guidelines specifically advise against

the use of NIPPV.17,34 The joint guidelines by the European Society of Intensive Care

Medicine and the Society of Critical Care Medicine advise against the use of NIPPV unless

HFNO is not available.19 NIPPV has been used successfully in COVID-19 patients in China

and Italy, as well as during the SARS epidemic in 2003. In Hong Kong, BiPAP was

effective in treating patients with SARS in 2003 with no identified healthcare worker

transmissions.39 However, there are other reports that use of BiPAP was associated with

increased rates of nosocomial transmission and higher rates of healthcare worker infection

in other situations.6

Additionally, the use of BiPAP and nebulizer treatments were associated with

outbreaks of SARS in hospital wards in China in 2003. In the same studies, high flow

oxygen masks (defined as flow rates >6 L/min) and mechanical ventilation were not

associated with nosocomial spread.40,41 These data may be of particular relevance to the

COVID-19 outbreak, where 3019 cases have already been reported in healthcare workers
including 5 deaths as of February 11, 2020.42 It is unknown if any of these were associated

with the use of any particular respiratory treatment.


These conflicting data suggest that BiPAP should be considered cautiously. Closed

circuit systems with appropriate filters in place are important, as are well-fitting masks and

the absence of facial hair on the patient, allowing for tight seals. Helmet BiPAP with an air

cushion in place around the neck is safe and should be used if available. All other forms

have been associated with higher dispersal distances than high flow oxygen systems and

concern for nosocomial and healthcare provider infection. Properly trained personnel are

also crucial.

4.3 Nebulizer therapies

Nebulizer treatments should be avoided in the care of patients with COVID-19. Jet

nebulizers were largely responsible for the spread of SARS in a hospital ward in China in

2003.12 The safety profile regarding APGs for these devices are extremely poor. Modeling

with human patient simulation shows that dispersion of particles could be measured beyond

0.8 m when flow rates mimicking severe lung injury were used (oxygen consumption of 500

mL/min, lung compliance 10 mL/cmH2O) (Figure 1).43

Jet nebulized therapies are possibly some of the highest risk events for nosocomial viral

transmission and should only be performed when absolutely necessary in negative pressure

environments with highly trained personnel. Some high flow/high velocity systems and

closed positive pressure systems have capabilities to add nebulized medications without an

increased risk of particle dispersal.

Alternatives to nebulizer therapies include use of metered dose inhalers, or nebulized

therapies performed in an adapted oral/nasal mask.44 While estimates vary due to

methodology, 4–6 puffs of a metered dose inhaler is the dose equivalent to a 2.5mg

nebulized dose of albuterol.45 Placement of a viral filter inline with a nebulizer likely

decrease the risk for nosocomial or healthcare worker infection but to our knowledge, no
studies have directly measured this effect.

4.4 Mechanical ventilation

Mechanical ventilation through an endotracheal tube may be necessary for patients with

frank respiratory failure or multisystem organ dysfunction. The role of mechanical

ventilation in COVID treatment is still unclear. While potentially effective, the clinical

indications for escalation to mechanical ventilation remain unclear.10 Furthermore, the


FIGURE 2 Proposed treatment algorithm for patients with hypoxia due to COVID-19
5 INTEGRATING RESPIRATORY THERAPY OPTIONS
process of endotracheal intubation produces high amount of AGPs, contributing to the risks

associated with mechanical ventilation. During the SARS epidemic in 2003, intubation was

strongly associated with disease transmission to healthcare workers (relative risk, 13.29;

95% CI, 2.99 to 59.04).34 Thus, the needs of the patient must be balanced against the

inherent risks associated with intubation and mechanical

ventilation as well as the risks to providers.

A joint statement by German Intensive Care, Anesthesia, and Emergency Medicine

Societies suggests direct escalation to intubation and mechanical ventilation if PaO2/FiO2 <

200 mmHg.18 A group of French experts recommended mechanical ventilation

implementation in patients expected to fail other oxygenation/ventilation strategies due to

respiratory failure or clinical deterioration (eg, shock, organ failure, etc) with the

symptomatic challenges of ARDS. 34 Importantly, observers in China have identified the

presence of hypoxemia without signs of respiratory distress (silent hypoxemia), especially

in elderly populations. During any respiratory management, patients should regularly be

monitored and checked for respiratory deterioration to prevent this occurrence.

There are no clear evidence-based guidelines for the ideal time to proceed to

mechanical ventilation in patients with COVID-19. Availability of ventilators, intensive

care capacity, considerations of palliative care and end-of-life resources as well as

individual patient characteristics all play a role in decisions to institute mechanical

ventilation.
Treatment of patients with COVID-19 whoare hypoxicshould follow the principles of treatment of hypoxicpatients resulting

from other etiologies (Figure 2). For patients with O2 sat <90% and mild to moderately increased work of breathing, consider

supplemental oxygen (NRB mask preferred) with goal of O2 sat >90%. For those with increasing work of breathing, worsening

hypoxia or failure to maintain O2 sat >90%, consider high flow oxygen (HFNO/HVNI). Reassess at least every 30 minutes for the

first hour, and then hourly for the next few hours. Monitor closely for clinical deterioration, and look out for the possibility of

“silent hypoxemia.”43
Proceed to mechanical ventilation in patients who do not respond to high flow oxygen (HFNO/HVNI) in the first 2 hours.

Criteria

include, but are not limited to: (1) need of vasopressor support,30,34 (2) persistently high respiratory rate, (3) persistent

thoracoabdominal asynchrony,35 or (4) low ROX index.36 Consider expert opinion in indeterminate cases. When in doubt, err on

the side of early intubation

If clinical findings are consistent with ARDS, hemodynamic instability, altered mental status, or severe hypoxia, proceed

directly to endotracheal intubation and mechanical ventilation, unless not available or not desired by the patient.

NIPPV should only be used if helmet masks are available, or if high flow oxygen systems

options are not available (summary in Figure 2).

6 CONCLUSION

The COVID-19 pandemic requires a more comprehensive risk-benefit analysis with

deciding the modality of respiratory support for patients. The risks for healthcare worker

infection, nosocomial spread, availability of resources, and clinical spectrum of disease must

all be considered.

CONFLICTS OF INTEREST

Jessica S. Whittle has served as a consultant to Vapotherm, Inc., within the last 3 years for

the development of educational materials. All compensation totaled less than $1000. Ivan

Pavlov has been a speaker for Fisher-Pakyel within the last 3 years. All compensation was

paid to the charitable foundation at the hospital where he works and he did not personally

receive any compensation. Alfred D. Sacchetti, Charles Atwood, and Mark S. Rosenberg

have no disclosures.

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