The management of the hypoxic COVID-19 patient has drastically shifted in recent weeks. Earlier expert recommendations pushed for early intubation of these patients in an attempt to minimize the risk to staff that is thought to happen with less invasive modes of oxygenation such as High Flow Nasal Cannula (HFNC) and Non-Invasive Ventilation (CPAP/BiPAP). Further, patients presented with rather profound hypoxia with radiographic findings similar to ARDS, and blanket treatments were initiated employing lung protective measures from ARDSnet. The problem is, this didn’t seem to help a large majority of patients the way we had thought it would and our focus has since shifted to avoiding intubation if at all possible. But is it safe to healthcare workers?
Enter the Phenotype Theory...
Gattinoni, et al., (published April 16, 2020)
Type L Phenotype (70%) – occurs early in the course
With these patients, a CT scan will primarily show only subpleural ground-glass changes along the lung fissures. The lung compliance, and therefore the amount of gas within the lungs, remains nearly normal. The ratio between ventilation and perfusion (V/Q ratio) remains low and their hypoxia may be explained by a loss of hypoxic vasoconstriction leading to a loss of the lungs ability to regulate perfusion. Further, recruitability is low as the amount of aerated tissue is still fairly well preserved.
These patients likely do best with conservative measures to improve oxygenation, such as with the use of High Flow Nasal Cannula instead (Grieco, 2019). A patient with a Type L phenotype may remain in this phase for an extended period of time before they improve or worsen. Our job as clinicians is to first do no harm. While this worsening could be due to the natural progression of disease, perhaps there is more to it. An inflammatory response in the lungs leads to increased permeability. With large tidal volumes, such as those used with positive pressure devices, or with an increase in the patient’s own inspiratory effort, there is a marked increase in intrathoracic negative pressure leading to interstitial edema. These patients still have a fairly preserved amount of aerated tissue in the lungs (meaning recruitability is low). The “silent hypoxia” patient many are describing seeing with early COVID-19 infections need oxygen more than they need aggressive positive pressure and we should tailor our oxygen escalation efforts accordingly.
Type H Phenotype (30%) – occurs later in the course
As interstitial edema worsens, the V/Q mismatch increases and the amount of gas aerating the lungs will decrease. Patients’ dyspnea worsens leading to increased inspiratory effort, increased negative intrathoracic pressure and worsening edema. The patient then transitions to Type H phenotype. Type H pattern fits the more classic ARDS appearance. There are diffuse bilateral infiltrates, a decrease in compliance and an increase in recruitability. This means that positive pressure can actually open up areas of the lung which have collapsed and more likely to be beneficial.
Therefore, we should not intubate these patients just based on the degree of hypoxia. Instead, escalation to mechanical ventilation should be based on the patients work of breathing, mental status changes and increases in PaCO2.
Aerosol Generation
For an-depth look at the literature of aerosols vs droplets and airborne spread of Influenza and Coronavirus, check out this article from First 10 EM. Further, this meta-analysis of 10 studies published in the journal of infectious disease shows droplets from coughs and sneezes can travel up to 8 meters with SARS-CoV-2 detected in the air up to 3-5 hours after aerosolization (Van Doremalen, 2020).
In a study from the University of Nebraska Medical center, SARS-CoV-2 RNA has been isolated all over patient rooms, their personal items, in the air ducts and even outside in the hallway suggesting aerosolized transmission (Santarpia, et al.). Just simple breathing, coughing and talking has been shown to expel droplets <2 μm in size, allowing them to remain suspended in air and travel great distances (Papineni, et al.). While the presence of viral particles doesn’t necessarily mean transmission is possible, it certainly supports our need to exercise caution to maximize protection to ourselves and our staff. Negative pressure rooms are an extremely valuable measure, when available. Each air exchange in a negative pressure room can remove up to 63% of all airborne droplets (Fiegel, 2006). However, since air doesn’t mix equally, this number may be as low as 20%. Employing precautionary measures to minimize aerosol development is therefore paramount for the health and safety of our staff.
Early recommendations to mitigate transmission of SARS-CoV-2 included avoiding High-Flow Nasal Cannula (HFNC) and Non-Invasive Positive Pressure Ventilation (NIPPV) as these measures have been shown to create aerosols. However, without these measures available to our patients, the ability to effectively treat them becomes significantly more challenging.
So, what exactly are the risks?
- Study Title: Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks.
- Purpose: Measured the dispersion distance of 20% normalized smoke concentration using heated HFNC at 10-60 LPM and compared this to CPAP at 5-20 cmH2O via nasal pillows (Respironics Nuance Pro Gel or ResMed Swift FX) or via an oronasal mask (ResMed Quattro Air) in a negative pressure room. Dispersion distance was revealed by laser-light sheet.
- HFNC Results: The average maximal dispersion distance with HFNC was ~17 cm and seen in patients with normal lung function. Certainly, this isn’t the population we are using this device on. Dispersion distance was less than half that in patients with diminished lung function. However, these numbers are dependent on proper fitting nasal pillows. With loose connection, maximum dispersion from HFNC increased to 62 cm at maximal flow rate of 60 LPM.
- CPAP Results: The minimal dispersion distance with the tested CPAP modes was in line with the maximal dispersion distance seen with HFNC. However, there were no significant leaks at all tested pressures. A properly fitted heated High Flow Nasal Cannula appears to be the safer option in regards to dispersion of aerosols, and therefore may be the safer option to minimize risk to staff. But what if the connection comes loose?
Is there a way to mitigate that risk?
I’m glad you asked…
Vapotherm Study (Leonar, et al., 2020)
- Study Title: High Velocity Nasal Insufflation (HVNI) Therapy in Management of COVID-19
- Purpose: Looked at high velocity nasal insufflation (HVNI) and aerosolization with HFNC in a standard non-negative pressure room with 6 air changes per hour. They performed a simulation with HFNC and a surgical mask on the patient to assess dispersion.
- Results: By placing a simple mask over a patient receiving High Flow therapy, 87.2% of particles were effectively filtered. Those that did leak around the mask, had a final path length of < 1 meter. Further, this was significantly less than a patient receiving no oxygen therapy and not wearing a mask.
Score a point in favor of masks...
But, what about other oxygen modalities?
- Study Title: High-flow nasal cannula for COVID-19 patients: low risk of bio-aerosol dispersion
- Purpose: Looked at the risk of aerosolization utilizing a smoke simulation via a manikin model.
- Results: Looking at the table, we see that high flow nasal cannula at maximal flow rate of 60 LPM actually has a lower dispersion distance than a non-rebreather or Venti mask.
How about another study...
- Study Title: Respiratory support for adult patients with COVID-19
- Methods: This study wasn’t a direct head-to-head study. Rather, it is a summary of multiple other studies looking at the Aerosol dispersion distances (cm) for various oxygen supplementation modalities.
- Results: NIPPV had the longest range of dispersal at 85-95 cm. Nebulized medications was a close second at 80 cm. Interestingly, High-Flow Nasal Oxygen has an average of ~5-17 cm with low flow nasal cannula reaching up to 40 cm in some studies.
Well, what else do I need to worry about?
- Study Title: Aerosol Generating Procedures and Risk of Transmission of Acute Respiratory Infections to Healthcare Workers: A Systematic Review.
- Methods: Systemic review of literature from 1/1/1990 to 10/22/2010 with outcome of interest being acute respiratory infection transmission.
- Results: Procedures that increase risk of transmission include endotracheal intubation, NIPPV, tracheotomy, manual ventilation before intubation. This is an older study, and therefore not exactly information that is new to us. Regardless, it is a nice review as 1 study looked at transmission of the original SARS causing virus with use of HFNC. The odds ratio was found to be 0.4.
Wait…Odds ratio…what does that even mean?
An odds ratio of 0.4 means that 0.4 people will transmit the virus for every 1 patient that does not. That translates to an average of 1 transmission event for every 2.5 non-transmission events. That calculated out to (does math…) a 28% chance of transmission if you are exposed to a patient receiving HFNC without proper protection. But don’t freak out. This is the lowest risk intervention on the list!
But wait, there's more...
- Study Title: Comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: a randomized controlled crossover trial
- Methods: Randomized controlled crossover non-inferiority study at a single multi-disciplinary ICU in China from October 2015 to April 2017. Evaluated degree of environmental contamination by viable bacteria associated with the use of HFNC compared to conventional oxygen mask for patients with Gram-negative pneumonia.
- Results: High-flow nasal cannula use was not associated with increased air or contact surface contamination by either Gram-negative bacteria or total bacteria.
- Study Title: Nasal high-flow therapy and dispersion of nasal aerosols in an experimental setting
- Methods: Aerosols within the exhaled breath of healthy volunteers were imaged. Experimental breathing conditions deemed as typical patient breathing conditions were tested: at rest, with a violent exhalation (snorting), both with and without NHF, at flows of 30 and 60 L/min, and for both separate nostrils.
- Results: The numbers of aerosols measured were greatest during a violent exhalation without HFNC and reduced with HFNC. The numbers of aerosols were higher at 60 than 30 L/min, suggesting that higher gas flow rates may be associated with increased aerosol production; however, the numbers were on average 43% and 56% less than without HFNC, respectively. During breathing at rest, no differences were imaged between with and without HFNC, except at 60 L/min where numbers of aerosols produced were equivalent to 10% of a violent exhalation. Aerosol trajectory and evaporation rates observed both with and without HFNC predicted that aerosols between 25 and 250 μm may travel up to 4.4 m and remain airborne for 43 seconds.
- Conclusions: HFNC use does not increase the risk of dispersing infectious aerosols above the risk of typical patient breathing with violent exhalation, which is the worst-case clinical
So, which is better for our patients....HFNC or NIPPV?
- Study title: High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure.
- Methods: Multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation.
- Primary outcome: The proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28.
- Results:
- 310 patients were included in the analyses.
- The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons).
- The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons).
- The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006).
- Conclusions: In patients with non-hypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality.
- Study Title: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.
- Methods: Single-centered, retrospective, observational study of 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) in Wuhan
- Primary outcome: 28-day mortality, as of Feb 9, 2020.
- Secondary outcomes: incidence of SARS-CoV-2- related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation.
- Results: 85% of those treated with HFNC survived, vs only 30% with NIPPV
- Limitations: This study didn’t specifically assess a head-top-head comparison of HFNC vs mechanical ventilation. At the time of this article, there was a push for early intubation. Perhaps those being intubated were sicker, and less likely to survive regardless of intervention?
- Study Title: The experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of Chongqing, China
- Methods: Unblinded retrospective study (can lead to selection and physician bias) of 318 patients (27 patients met criteria for severe respiratory failure needing HFNC or NIV.
- Results:
- HFNC 1st Line: 17 patients
- NIV 1st Line: 9 patients
- Invasive Ventilation 1st Line: 1 patient
- 7/17 (41%) HFNC 1st patients experienced HFNC failure
- 2/7 (29%) failed NIV and required intubation
- HFNC failure rate:
- PaO2/FiO2 > 200mmHg: 0/6 patients (0%)
- PaO2/FiO2 ≤200mmHg: 7/11 patients (63%)
- p = 0.04
- Respiratory rate significantly decreased after 1-2 hrs of HFNC in successful group:
- Median 26 vs 23 compared to the unsuccessful group (p = 0.03)
- Conclusion: HFNC non-inferior to NIV for intubation rate. HFNC more comfortable than NIV for patients. Manipulation of HFNC is much easier than NIV.
Well, what do the guidelines say?
ANZICS guidelines on COVID-19: “High flow nasal oxygen (HFNO) therapy (in ICU): HFNO is a recommended therapy for hypoxia associated with COVID-19 disease, as long as staff are wearing optimal airborne PPE. The risk of airborne transmission to staff is low with well fitted newer HFNO systems when optimal PPE and other infection control precautions are being used. Negative pressure rooms are preferable for patients receiving HFNO therapy.”
Surviving Sepsis Guidelines: “For acute hypoxemic respiratory failure despite conventional oxygen therapy, we suggest using HFNC over conventional oxygen therapy (weak recommendation, low quality of evidence).”
WHO guidelines on COVID-19: “Recent publications suggest that newer HFNC and NIV systems with good interface fitting do not create widespread dispersion of exhaled air and therefore should be associated with low risk of airborne transmission.”
ESICM guidelines: Suggests using oxygen delivered by HFNC as first-line therapy for patients with COVID-19 and acute hypoxemic respiratory failure in preference to NIPPV/CPAP, although the latter could be used “with close monitoring and short-interval assessment for worsening respiratory failure.” However, these are not recommendations, just suggestions, only supported by low-quality evidence, the society notes.
Bottom Line: The scientific evidence of generation and dispersion of bio-aerosols via HFNC summarized above show a similar risk to standard oxygen masks and significantly lower than even that of a normal cough. HFNC prongs with a surgical mask on the patient’s face is a very reasonable practice to avoid intubation in patients with COVID-19. HFNC appears to be at least non-inferior to NIPPV and may even offer survival benefit.
For further discussion on delayed intubation and initial ventilator modes, check out this article by a lot of well-known critical care docs.
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