Respiratory Support For Adult Patients With Covid
Respiratory Support For Adult Patients With Covid
Respiratory Support For Adult Patients With Covid
Jessica S. Whittle MD PhD1 , Ivan Pavlov MD2 , Alfred D. Sacchetti MD3,4, Charles Atwood
Tennessee, USA
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
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
1 INTRODUCTION
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
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
balance the clinical benefit of the intervention against the risks of nosocomial spread.
commits to the prolonged use of an ICU bed and mechanical ventilator, which may not be
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
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
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
oxygen saturation >90%. The target of treatment should be SaO2 = 92%–95% for pregnant
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
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
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
COVID-19 patients as the mask helps to limit the dispersion of droplets. NRB masks can
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
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
risk of subsequent intubation (relative risk [RR] 0.85, 95% confidence interval [CI]
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
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
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
There is no currently published evidence that HFNO is a risk factor for nosocomial
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
For the treatment of pneumonia, HFNO was associated with reduced mortality
conventiona lnasal cannula. Of those 20 patients, 9 were successfully treated with HFNO
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%)
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
recommendations.37,38
(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
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
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
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
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.
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
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
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.
Mechanical ventilation through an endotracheal tube may be necessary for patients with
ventilation in COVID treatment is still unclear. While potentially effective, the clinical
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
Societies suggests direct escalation to intubation and mechanical ventilation if PaO2/FiO2 <
respiratory failure or clinical deterioration (eg, shock, organ failure, etc) with the
There are no clear evidence-based guidelines for the ideal time to proceed to
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
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
6 CONCLUSION
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.