Dr. Cameron Kyle-Sidell is an ED-ICU Doc at Maimonides in New York, currently under the COVID fire. He put up an inflammatory tweet yesterday which caused a lot of different reactions, because it clearly challenged the widespread even if only recent belief that one should intubate the COVID patients quite early, usually much earlier than one would in typical respiratory failure:
So here you go:
Please share your thoughts and experiences – my comments in bold!
Korbin Haycock:
Very interesting. My experience is zero cases so far with COVID-19. Just some thoughts for what it’s worth from someone with no experience with COVID: Hypoxia is due to V/Q mismatch, diffusion, hypoventilation, low pO2 (altitude), shunt, low cardiac output (as more O2 is extracted off HgB and mixed venous O2 is low), and finally hemoglobin problems (whether by poisoning or defective HgB).
It was pointed out to me by Brett Berliner tonight in a paper (via twitter) that SARS CoV-2 appears to disrupt the beta chain of HgB to take up O2. I’d never heard of this, but if this is the case, exchange transfusion makes sense as a therapy for hypoxia as long as one is past the stage of illness where the viral levels are low. If this is a hemoglobinopathy, no amount of increase in mean airway pressure or FiO2 will fix the hypoxia.
Perhaps people out there with actual experience with COVID-19 can shed additional light on how the hypoxia tends to respond to positive pressure or increases in FiO2, or more importantly a lack of expected response, that would indicate the mechanism of hypoxia (such as a hemoglobinopathy).
It is very interesting that the hypoxic patients described in the post don’t appear to be very symptomatic in terms of SOB, nor do they attempt to compensate for the ding to DO2 from low O2 sats (O2 content) with an increase in HR to drive up CO. Normally DO2/VO2 ratios are around 4-5, so either the illness suppresses the normal physiological response to a decrease in the ratio, or the VO2 is suppressed somehow (seems unlikely). In any event, perhaps we should revisit the idea to intubate early if hypoxic, unless the patient actually looks really bad.
Summer Allen:
I’m Pulm/cc. This was fascinating and sparked some ideas. But, I need someone smarter than me to take it forward. The first thought is this is not what we know. It’s a different beast. Stop trying to make it fit what we know.
Why are people not short of breath or tachycardic? I suspect most of this is that compliance is high and there is no issue with expiratory flow limitation, hence WOB is more or less normal… And once hypoxia is corrected with O2, they feel fine.
Does the virus hide hypoxia from the body? Maybe it turns off normal feedback that would make us short of breath and tachycardic. The body doesn’t compensate because it doesn’t know it’s hypoxic. That’s why people are being found dead at home because they didn’t know they were slowly suffocating. Maybe it’s not affecting kids because their feedback mechanisms are more heightened already because of growth. Trying to think outside of the box after listening to this. I definitely agree that treating these patients like normal pneumonia with vent/pressors/fluids isn’t the answer.
Bala Totapally
Looks like these pts have severe V/Q mismatch without abnormalities in respiratory mechanics. Almost like a cyanotic heart condition. I agree if the mechanics are not worsening we may not achieve a lot by early intubation except to prevent sudden deterioration, if anything. HFNC with 100% will be the right choice. Has anyone tried nitric oxide before intubation? Might work to improve V/Q mismatch and reduce RV strain.
I am definitely planning to look at RV function and use inhaled vasodilators both for the VQ and for RV function.
Richard Harper:
Great talk and very fascinating points. Short of hyperbaric chambers for everyone, I think keeping everyone on high flow for as long as possible seems very reasonable. Given the ongoing reports I’m seeing regarding the pathophysiology regarding COVID-19 related lung disease, including your shared observations, it seems like using stress index on intubated patients would be the best measure of appropriate PEEP in this setting without “trashing” the lungs. If our understanding is correct regarding the atelectatic, high compliance Sars-cov-2 lung is correct, then the PEEP table is not going to accurately predict the proper settings and the stress index measured once a day would solve the problem of too much PEEP.
stay safe!
Philippe
thinking critical care 
Very interesting. My experience is zero cases so far with COVID-19. Just some thoughts for what it’s worth from someone with no experience with COVID: Hypoxia is due to V/Q mismatch, diffusion, hypoventilation, low pO2 (altitude), shunt, low cardiac output (as more O2 is extracted off HgB and mixed venous O2 is low), and finally hemoglobin problems (whether by poisoning or defective HgB).
It was pointed out to me by Brett Berliner tonight in a paper (via twitter) that SARS CoV-2 appears to disrupt the beta chain of HgB to take up O2. I’d never heard of this, but if this is the case, exchange transfusion makes sense as a therapy for hypoxia as long as one is past the stage of illness where the viral levels are low. If this is a hemoglobinopathy, no amount of increase in mean airway pressure or FiO2 will fix the hypoxia.
Perhaps people out there with actual experience with COVID-19 can shed additional light on how the hypoxia tends to respond to positive pressure or increases in FiO2, or more importantly a lack of expected response, that would indicate the mechanism of hypoxia (such as a hemoglobinopathy).
It is very interesting that the hypoxic patients described in the post don’t appear to be very symptomatic in terms of SOB, nor do they attempt to compensate for the ding to DO2 from low O2 sats (O2 content) with an increase in HR to drive up CO. Normally DO2/VO2 ratios are around 4-5, so either the illness suppresses the normal physiological response to a decrease in the ratio, or the VO2 is suppressed somehow (seems unlikely). In any event, perhaps we should revisit the idea to intubate early if hypoxic, unless the patient actually looks really bad.
I can’t understand why no one is mentioning the use of hydroxychloroquine so that patients don’t progress to such a bad state. Please view these videos….
“The drug saved my life (in 5 hours!).” https://youtu.be/wLOi4I2mJLI?t=2m (8 minute video)
3/28/20 – 700 Patients, ZERO deaths, ZERO intubations – Giuliani / Dr.Zelenko interview –
Hydroxychloroquine/Zithromycin/Zinc Combo Proves Effective on 700 NY Patients – Dr. Vladimir Zelenko shares a preliminary study outlining how out of all the patients he treated, there were ZERO deaths, ZERO intubations https://youtu.be/1TJdjhd_XG8?t=1m24s (40 mins)
4/3/20 – Dr Corsi interviews Dr Vladimir Zelenko & Dr. Karladine Graves – HCQ Protocol To Win Virus War https://www.youtube.com/watch?v=Z7SDemHGl8U
The FDA has approved the use of HCQ but only in hospitals where patients are already very ill. If they would allow doctors to prescribe it outside hospitals to high risk cases and the elderly before they develop respiratory distress, they could prevent the need for hospitals and ventilators.
I’m Pulm/cc. This was fascinating and sparked some ideas. But, I need someone smarter than me to take it forward. The first thought is this is not what we know. It’s a different beast. Stop trying to make it fit what we know. Why are people not short of breath or tachycardic? Does the virus hide hypoxia from the body? Maybe it turns off normal feedback that would make us short of breath and tachycardic. The body doesn’t compensate because it doesn’t know it’s hypoxic. That’s why people are being found dead at home because they didn’t know they were slowly suffocating. Maybe it’s not affecting kids because their feedback mechanisms are more heightened already because of growth. Trying to think outside of the box after listening to this. I definitely agree that treating these patients like normal pneumonia with vent/pressors/fluids isn’t the answer.
If the Corona virus turns the lungs fibrous. Why are they not treating it as if the patient has Cystic Fibrous? This would make sense. Also, think outside the box and treat them using Hyperbaric Chamber with 100% Oxygen! Another treatment is salt air this helps break up phlegm/ fluid in the lungs. Along with percussion therapy.
Hello: looks like these pts have severe V/Q mismatch without abnormalities in respiratory mechanics. Almost like a cyanosis heart condition. I agree if the mechanics are not worsening we may not achieve a lot by early intubation except to
Preventing sudden deterioration, of any. HFNC with 100% will be the right choice. Have anyone tried nitric oxide before intubation. Might work to improve V/Q mismatch and reduce RV strain.
Here’s an article by a couple of Chinese PhDs or similar discussing the effects of the virus on hemoglobin. https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173 They mention chloroquine having an effect on porphyrins. Sure enough, cholorquin is used successfully on porphyria, and porphyria causes kidney damage.
Maybe hyperbaric chambers would be better treatment, similar to the way altitude sickness and the bends are treated. Concentrated oxygen pressure instead of mechanical ventilation.
Sure. Should start building them. Could make big ones and cohort patients.
[…] Here’s another idea from an NYC ICU doctor about when to intubate<— […]
Thank you for this very, very interesting and eye opening discussion.
Is there a way for us to contact Dr Kyle Sidell?
Lionel Lee, DO, FACOEP
drlionel@gmail.com
As a retired Nephrologist, this smacks of a perturbation in the renin-angiotensin system (RAS). We know the SARS-CoV2 binding site is the ACE2 receptor. ACE2, a respiratory endothelial receptor, is vital in the balance of arteriolar resistance in opposition to ACE. Changes in this balance are known to be age-related, diabetes related, and X-linked. Children and pregnant women have a highly protective ACE2 status. What you are seeing is intrapulmonary shunt related to diminished ACE2 availability and a runaway RAS.
Very interesting… will email you.
Dr. Sage: Million PhD 907-617-1337 engineering@techemail.com Dr. Kyle Sidell contact me ASAP
Can we learn more about this physiology from ECMO COVID patients? It seems like that would be the ultimate way to separate problems with gas exchange from oxygen carrying capacity problems. Has a patient with very low SpO2 like this been put on VV ECMO with a rapid improvement in SpO2, refuting the contribution of hemoglobinopathy? Has a patient with very low SpO2 like this still had a low SpO2 after initiation of ECMO and confirmation of a supranormal PaO2?
Very interesting. Two questions I have after your talk:
1. If this is hemoglobin problem, can you check pre- and post-oxygenator PaO2 level in patients with COVID-19 and VV ECMO? Because the oxygenator will not fix the hemoglobin problem, so if the PaO2 did not increase significantly after oxygenator, that would support your idea.
2. Can we transfuse RBC to help with oxygen carrier capacity? Since we are trying to get patients another day of ventilation-free, maybe transfusion with good blood (young blood – not old) will help these?
Thanks for listening! 1. I don’t have ECMO at my shop. 2. sounds reasonable. we will run out of blood!
I am Peds and trying to consider similar analogies.
First oxygen delivery. Is there a problem with the hemoglobin that carries oxygen. Does the virus sever iron from the heme molecule?
https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173 Most of this comes with three-D modelling of binding sites, not clinical but…
Does high ferritin, porphyrin or free iron toxicity cause this picture? Exchange transfusion, Chelation?
Chloroquine may have a role in porphyria? Supposedly competes with porphyrin for binding site of Virus.
Is the oxygen association curve being changed.? Does this virus change 2,3-BPG effects, (People with lower BPG more susceptible to High Altitude Pulm Edema. )
Does it keep hemoglobin in taut form, not willing to accept new oxygen?
Does it block and oxygen binding site, opposite of CO, that given and artificially low POx,
Would hgb electrophoresis, full spectrum absorption give any clues? Porphyrin absorbs at 410, while oxygen-hemoglobin at 940 and deoxy-Hbg at 660 nm.
Hydroxyurea provokes Hbg F production, improving sickle cell hemoglobin , but unsure of timeframe.
Second, airway. Parts of the descriptions seem similar to Persistent Pulmonary HTN of the newborn. Endothelial damage gives overproduction of endothelin. Treatment with iNO, PDE5 inhibitors.
We also use High Freq Oscillation Vent, the ultimate in “low” Tidal Volume
I know all of this is crazy, just throwing ideas out.
Dr. Kyle-Sidell. You previously asked if this is a lung disease or blood disease. Please think along the lines of blood disease as well. There has been a line of thinking toward chloroquine and some in-vitro evidence that it mitigates the damage caused by SARS-CoV-2. Chloroquine binds to hemoglobin and there is evidence that blocks the damage done to hemoglobin in the presence of the virus. A new preprint shows how: https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173
HCQ is being used widely and also trialed. real studies are not encouraging so far – there is a lot of garbage claims – but more time will tell.
I’m a retired general internist, so haven’t been “in the trenches” since I trained at Harlem Hospital in the early ’70’s. I greatly admire all of you – your courage and your thinking. I find this discussion both fascinating and enormously important. I have a few thoughts. I like the idea of using ECMO to differentiate between an O2 delivery vs O2 transport problem. The hemoglobinopathy hypothesis strikes me as interesting but a little too complicated. Basically, it seems like you’re dealing with waterlogged lungs because of leaky alveolar-capillary membrane damage. My thought is that what primarily damages the membrane is almost like a Herxheimer reaction caused by a massive flood of IgG antibody hitting lung parenchyma coated” with virus (remember SARS-Covid2 is 15 times “stickier” to ACE2 than SARS “classic”). That immunologic “storm” is what results in the bilateral ground glass appearance on imaging and also results in the V/Q mismatch. I agree that minimizing vent time, keeping the FIO2 high and the PEEP as low as possible makes sense to me – we learned that at Harlem “back in the day”. A couple of other thoughts – ARDS is not a disease, it’s a description. And these patients are in “distress” – one of the cardinal symptoms of severe disease, a criteria for a patient going to the hospital in the first place – is shortness of breath, i.e dyspnea. The tachypnea is the physiological response to the hypoxia, although I can’t explain the tendency to no or minimal tachycardia under the circumstances. I find the description of the “light-switch” sudden improvement described in the talk in some patients fascinating — it suggests the storm analogy – acute in its onset, severe during its course, sudden in its ending. If you can see the patients through the storm without damaging their lungs with high pressure ventilation, they’ll have a chance.
Although, I am a retired health care provider, this would always be way above my pay grade. Yet, I ask sincerely – what about ozone therapy? Would it address the hypoxia? Also, are there any further insights into the hemoglobinopathy?
ozone is highly toxic to cells. it would not be an option.
If you contact Dr Zach Bush (ZachBushMD.com), he can talk with you about a couple different potential reasons for high populace concentrations of Covid-19 and for increased vulnerability with patients.
If the worst and most prolific cases are in locations of high air pollution, including cyanide in the air, and / or high glyphosate spray, then can toxicity be affecting the body’s ability to clear C02 and to have sufficient effectiveness of oxygen in the system?
I have no medical background, and I looked up cyanide poisoning and found this quote interesting: “Hydroxocobalamin will detoxify cyanide by binding with it to produce nontoxic vitamin B-12. This medication neutralizes cyanide at a slow enough rate to allow an enzyme called rhodanese to further detoxify cyanide in the liver.”
https://www.healthline.com/health/cyanide-poisoning#complications
If this idea of toxicity being a factor makes any sense or helps connect the dots, that’s great. I totally respect Dr Kyle-Sidell’s observations and thoughtful considerations as well as your helpful interview. Your brilliant open minds and careful observations give hope for solutions.
You have my prayers and best wishes for all the insights needed.
Jeanine
@jrd1776 on Twitter
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