REBEL Cast Ep93: COVID-19 – A Follow Up on Not Intubating Early and ARDSnet

Back in April 2020, on REBEL Cast episode 79 we sat down to discuss COVID-19.  Specifically, we focused on not intubating patients early and why ARDSnet may not be the best ventilator paradigm for patients with COVID-19.  By popular demand, we decided to follow up on this podcast.  We are now just about 9 months since we recorded this podcast and I wanted to sit down with the same group and see if they had any amendments, they wanted to make regarding what we discussed.

REBEL Cast Ep93: COVID-19 – A Follow Up on Not Intubating Early and ARDSnet

Special Guests:

 

David A. Farcy MD, FAAEM, FACEP, FCCM
Immediate Past President of the American Academy of Emergency Medicine
Chairman, Department of Emergency Medicine
Director, Emergency Medicine Critical Care
Mount Sinai Medical Center
Miami Beach, FL
Twitter: @DFarcy

Evie Marcolini, MD, FAAEM, FACEP, FCCM
Associate Professor of Emergency Medicine and Neurocritical Care
Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
Board of Directors, American Academy of Emergency Medicine
Twitter: @EvieMarcolini

Cameron Kyle-Sidell, MD
Critical Care Medicine
Emergency Medicine
Maimonides Medical Center
Brooklyn, NY
Twitter: @cameronks

US Expanded Access Program:

  • Paper: Joyner MJ et al. Effect of Convalescent Plasma on Mortality Among Hospitalized Patients with COVID-19: Initial Three-Month Experience. medRxiv 2020 [1]
  • >1800 hospitals across the US
  • > 47k patients enrolled in EAP

Has anything changed regarding the use of high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV)?

  • We are keeping more patients on HFNC and not paying as much attention to SpO2
  • Despite the fact that HFNC has been proven to be safe, we still see a trend of increased intubations in some other countries
  • There is more data on the progression of patients that are not intubated, so we are becoming more comfortable with not intubating early
  • Institutions are more comfortable dealing with aerosolization concerns, thus we are more comfortable with the use of NIV
  • In the past, we were restricted due to high patient volumes, full ICUs and resource limitations. Now that we have lower numbers of patients, we are better able to weigh the risks and benefits of early intubations

What markers are we using to make our decisions to intubate?

  • Before COVID, tachypnea, tachycardia and SpO2 would be used to make decisions about intubation. Now we’ve added other considerations like mental status, diaphoresis and work of breathing
  • Patients on HFNC don’t seem to be tiring out the way we would typically expect. There are also discussions about the potential role of a new entity referred to as patient self-induced lung injury (P-SILI)
    • The concept is that you can have the same swings in intrapleural pressure with vigorous breathing as you would have with a ventilator. So while the breathing may appear fine, the heavy swings in pressure can cause lung injury. So theoretically, intubating a patient would be protective against this form of lung injury
  • Farcy: Our early data shows that patients with severe COVID who were maintained on HFNC without intubation have had length of stays of about 11 days with a 90% success rate. Some reports state that lung injury may be due to microthrombi. There are also some reports of steroids and aspirin decreasing mortality

Thoughts on pathophysiology of COVID-19?

  • Regarding the pathophysiology, some intensivists have drawn parallels between COVID and acute fibrinous and organizing pneumonia (AFOP). This is a disease with a slow progression that responds to steroids, but a patient can also suddenly deteriorate. The strategy in AFOP is usually to monitor work of breathing
  • Marcolini: Fatui et al also discusses stages of the neurological manifestations of COVID. Applying this framework, we ask ourselves, where is our patient in the progression of the disease
    • In the first stage, the virus stays in the nasal passages and there is no cytokine storm or entry into the brain
    • In the second stage, you have a cytokine storm that causes inflammation and hypercoagulability in addition to neurologic symptoms
    • In the third stage, the cytokine storm explodes, and you have a huge systemic inflammatory response
  • Kyle-Sidell: Work of breathing is inherently tied to compliance. Patients that we thought would tire out, don’t, due to having a preserved lung compliance. We have patients with poor P/F ratios, but they have higher tidal volumes than we would expect.
    • Through intubation and the use of high PEEP, we are trying to increase recruitment in the lungs. However, in patients with COVID, we are causing over-distension of alveoli which were already damaged due to the vascular effects of COVID. (We now know that this disease is primarily a platelet-driven, endothelial-activated vascular process
    • Some people consider COVID a heterogenous disease, however if we put aside the complications, it is relatively uniform in terms of pathophysiology. The heterogeneity is in the time-frames and severities that patients present with. So depending on the time-frame of when the complications present, the management can change. Although best management is not always clear, we do need to take into consideration what is going on in the patients’ lungs and how to best address that
  • Farcy: We try to manage patients with HFNC and proning as long as they are mentating appropriately and do not have an increased work of breathing. For those who are intubated, we give steroids and aspirin. With this, we have seen less cytokine storm than in patients that were intubated early. I think the gradual escalation of therapy may have helped curb the severe cytokine storm that is associated with multi-system organ failure in patients with severe disease.

Putting it all together

  • Time does matter. COVID is a heterogenous disease because we don’t know what those timeframes are along its natural progression. There is a viremic phase, followed by a pulmonary phase, followed by a hyper-inflammatory phase
  • We are mostly seeing patients on days 5 -10 by the time they come in to the ED, which corresponds with the pulmonary phase
  • We are in agreement that we should avoid intubating early. But with the added consideration that there may be patient-induced lung injury in patients we manage on HFNC and NIV for too long, a theory that is yet to be proven
  • Despite considering COVID an alveolar disease earlier this year, the thinking has now changed to COVID being a vascular disease associated with endothelial injury and platelet hyper-activation. So putting people on high tidal volumes and high PEEP can over-distend damaged alveoli and cause more injury. And this may be one of the reasons for the hyper-inflammatory, multi-organ failure we see in patients that were intubated early

If you had to choose between HFNC and NIV, which would you choose and why?

  • HNFC is preferable initially for several reasons:
    • BiPAP at high settings is more aerosolizing than HFNC at any setting
    • While useful in ARDS due to regional collapse, NIV has not been as useful in COVID because there seems to be a different pathophysiology
    • In the absence of helmets, NIV masks are harder to tolerate for patients for a week or more. With nasal cannula, patients can still eat and they are generally more comfortable.
  • Marcolini: If a patient is hypoxic, I go with HFNC. If they are hypercarbic, I am thinking about BiPAP
  • If a patient on HFNC is found to have significant collapse on CT without consolidation, it would make sense to then progress to NIV.
    • Assuming that you have the staff to monitor them appropriately.

It appears that COVID starts with a higher compliance and air-filled alveoli and then transitions to a more traditional ARDS with a lower compliance where recruitment and proning would be helpful. What are your thoughts?

  • Although proning appears to improve SpO2, it does not seem to increase recruitment in a significant way. And an additional benefit of repositioning is the shifting of oxygenation and blood flow that potentially prevents ischemia to lung segments
    • When proning is typically used in the ICU on non-COVID diseases, we do see some sustained recruitment in the form of improving P/F ratios. In COVID patients, however, that has not been the case
  • Kyle-Sidell: I was initially not using NIV partly because we didn’t have negative pressure rooms or staff to watch the patients. But some patients managed with HFNC do progress to a low-compliance, non-recruitable state. These are patients that if stable enough, young enough and at the right center, could be considered for ECMO or lung transplantation
  • Proning should still be used at all stages of COVID.
    • Early stages: Shifting of blood flow to areas with less damage (COVID most often affects the posterior lower segments)
    • Late stages: some beneficial recruitment in the lungs
    • Allows for the use of less aggressive interventions with less oxygen and lower pressures
  • Farcy: I have some patients being managed at home with HFNC who report dramatic improvements to SpO2 with proning. However, their SpO2 drops again when they leave the prone position.

What are the triggers to intubate? Have they changed since we last talked?

  • Kyle-Sidell: The initial threshold we had for intubation was when they required 100% FiO2 to achieve a SpO2 of 88-90% combined with distress (defined as anxiety and tachypnea), or sustained SpO2 levels below 80%. We then learned that when a patient knocks off their nasal cannula and goes down to 29% SpO2, to just leave them there and replace the nasal cannula and let them come up again before getting respiratory therapy involved. The only thing that has changed for me is wondering whether or not I am waiting too long to intubate. I am constantly thinking about whether or not there is a way to protect the patient’s lungs
  • We’ve stopped looking at numbers or following SpO2, so no changes to our approach since then

Take-Home Messages:

  • Early intubation should still be avoided
  • Consider mental status and work of breathing when thinking about intubation
  • In a stable patient, HFNC should be attempted first, followed by NIV for patients that require more support
  • Proning is still beneficial at all stages of COVID

References:

  1. Joyner MJ et al. Effect of Convalescent Plasma on Mortality Among Hospitalized Patients with COVID-19: Initial Three-Month Experience. medRxiv 2020. [Epub Ahead of Print]

Transcript By: Yasien Eltigani, MS4 at St. George’s University (Twitter: @yasieneltigani)

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)

Cite this article as: Salim Rezaie, "REBEL Cast Ep93: COVID-19 – A Follow Up on Not Intubating Early and ARDSnet", REBEL EM blog, December 19, 2020. Available at: https://rebelem.com/rebel-cast-ep93-covid-19-a-follow-up-on-not-intubating-early-and-ardsnet/.
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Salim Rezaie

Emergency Physician at Greater San Antonio Emergency Physicians (GSEP)
Creator & Founder of REBEL EM

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4 thoughts on “REBEL Cast Ep93: COVID-19 – A Follow Up on Not Intubating Early and ARDSnet”

  1. I am not a doctor, just an interested lady who is now 63 with COPD.
    Cameron I dont know how I found you at the beginning of all this but it has been fascinating to follow you and learn about all this stuff. And thanks for going against protocol and speaking up.
    Dr, Farcy Thank You too. I think its crazy awesome that PPE is working that well.!
    Dr, Evie Marcolini Thank you too for all you do. Trust the PPE.

    Michele in Florida

    Reply
  2. Thanks to all the contributors. It’s good to hear some voices doing critical analysis of the dominant narratives. I have been following Dr. Kyle=Sidell since his “high altitude sickness” days.

    Disclaimer: I have no medical training other than having read over 100 covid-related papers. 20+ hours of biology including micro and biochem, BA (chem), and MS (physics) with thesis, so understanding the papers is no problem for me. My vascular surgeon daughter lives with us, so I can run my thoughts by her to find errors in my thinking.

    Reply
  3. This is a nice review in an area we don’t have much evidence.

    But I think we do have evidence now that does not support some of the more dogmatic claims made here.

    For example, we now know from published studies (https://www.thelancet.com/action/showPdf?pii=S2213-2600%2820%2930370-2, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30525-7/fulltext) that lung compliance in intubated covid pts is not really any different than in those with traditional ARDS. We are fooled at times because of the hyperperpnia and large TV’s they want to take, but once those pts are intubated sedated and receive NMBs you will see that their static compliance isn’t great and does resemble traditional ARDS. This supports treating them as we treat traditional ARDS pts at least in terms of ARDSNet tables and prone positioning.

    Also, the idea that these pts have a “cytokine storm” is probably not really true. There may be select pts who truly do develop a secondary HLH syndrome, but that would not be the norm, even for severe/critical COVID-19 pts. There have been several reviews published over the last 4 months showing that cytokine and inflammatory marker levels actually aren’t much different in COVID-19 than in other typical ICU pts (septic shock, non-covid ARDS, trauma) and are quite a bit lower than hyperinflammatory states such as CRS (https://www.thelancet.com/action/showPdf?pii=S2213-2600%2820%2930404-5, https://jamanetwork.com/journals/jama/fullarticle/2770484).

    I think the major difference with COVID-19 may not be related to excessively high inflammation, but about persistent/prolonged inflammation. As you all note the duration of illness here is much longer than typical viral PNA. For ex influenza is usually 1-3 days from onset of sx to respiratory failure, vs 6-12 days with COVID-19. And this slower more indolent presentation I think does allow pts to accommodate better and push themselves further and not rapidly decline as quickly and consistently, and all this allows us to push them further on HFNC without intubating.

    But despite all the anectdote expressed on here and by others I do not think we really know if we are helping pts by keeping them on HFNC for prolonged periods of time compared to intubating them. And I do not think intubating someone with significant hypoxemia, even without increased WOB, is necessarily wrong. I do believe that placing pts on NIPPV for hypoxic respiratory failure due to COVID is NOT appropriate for multiple reasons (can’t expectorate, eat, breakdown on face, less control over TV/pressures than if intubated, and propensity for these pts to get FiO2 and PEEP up-titrated and by time you have to intubate them for failure they are on 100% and PEEP 10 with SPO2 80% and now very physiologically-risky to intubate with high chance of arrest).

    I think giving more consideration to total plasma exchange earlier may be appropriate as well, and when coupled with early intubation may prevent self-inflicted lung injury as well as O2 toxicity from prolonged HFNC and by squelching the process quickly with TPE the pt may be extubated in <7 days mitigating the harms of prolonged intubation with high levels of sedation/NMB. But at this point there isn't a lot published on this, and that is more of my anecdote.

    Also, on followup of those discharged, irreversible fibrotic processes are not being noted with any significance, but organizing PNA (COP, AFOP) is (https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.202008-1002OC).

    And although there is endothelial injury/platelet hyperreactivity/high serotonin (see Dr. Farid), this does seem to be an alveolar process, at least that is where it all starts after leaving the nasopharynx, see this recent study for great read on proposed pathophysiology of covid-19 (https://www.nature.com/articles/s41586-020-03148-w)

    Reply
    • Hey Phil,
      Appreciate the comments. Agree with the majority of what you say…I think there is still a lot to be proven and each of us is trying to wrap our brains around what is best for patients. 100% agree with your comments on NIV, not sold on plasma exchange (although I could be proven wrong), and finally the struggle is real on when to pull the trigger for intubation. In my mind this is the biggest grey area and have yet to hear or read a solid answer to this question. TY for taking the time to read/listen and leave your thoughts. Stay safe.

      Salim

      Reply

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