UKC

The recent RECOVERY trial (Randomised Evaluation of COVid-19 thERapY) press release widely reported in the mainstream media claims that dexamethasone - a drug familiar to mountaineers for its treatment of high altitude illness - reduces death by up to one third in ventilated patients with severe respiratory complications of COVID-19. Prior to this 'major breakthrough', some physicians - and climbers in our forums - were pondering the similarities between the breathing difficulties and persistent cough commonly displayed by COVID-19 patients and the symptoms experienced by HAPE (High Altitude Pulmonary Edema) sufferers on high peaks.

We contacted critical care consultant and mountaineer Jeremy Windsor to find out more.

What a great article. I admit I was a bit sceptical before reading it due to the headline style title but that was brilliant. Enough detail from a expert for the interested layman without being overwhelming, a good synopsis of the research and a nice personal "Op Ed" style final two paragraphs.

Quality work UKC, well done.

So not fully proven but available, in use and it appears, saving lives.  Every little helps in this current fight. Well worth the read.

Good article, well done UKC for such and informative and balanced report. 

Very helpful article. 

I'm glad the potential immunosuppressive effects of steroids are mentioned.  I've read a few comments suggesting that it was obvious to use something like dexamethasone once the importance of the inflammation was realised, but using steroids in the presence of an active viral infection can run a real risk of making the infection worse.  Of course, not all steroids are the same, but still, it's a slightly counter-intuitive thing to do. 

This UKC article is great news but this one isn't I'm afraid.

https://www.theguardian.com/us-news/2020/jun/30/us-buys-up-world-stock-of-k...

'Looking after your own?'

The (un-peer reviewed) preprint of the article is here: https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1

There's another aspect of this - if you are coming up against a cytokine storm, suppressing the immune system might well be what you actually do want to do at that stage.

"Many of these are young people, often with young families, working in the NHS or other caring professions,' Jeremy explained."

"Young" is subjective, but only 8% are under 40, see ICNARC's COVID-19 Report, https://www.icnarc.org/DataServices/Attachments/Download/0a0738a6-dcb7-ea11...

​​​​​​Dexamethasone is an exceptionally well known drug having been in use for decades. It has few severe side-effects, essentially, you may as well prescribe it for these patients. https://bnf.nice.org.uk/drug/dexamethasone.html

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Is there anything that man won't do to win votes.  Of course his real motivation was to save American lives. 

In other news...

https://www.gov.uk/government/publications/medicines-that-cannot-be-paralle...

(Dexamethasone added as of 16/06/20)

I'm not sure what the distinction between buying all of the stock and preventing export is, but superficially at least there does appear to be a similarity.

There is quite a large difference.

Remdesivir is an on-patent drug meaning that its manufacture is strictly controlled by Gilead (the pharmaceutical company that owns the patent).

Dexamethasone (and numerous other corticosteroids) are no longer on-patent and can be manufactured by any pharmaceutical manufacturing company (subject to regulatory compliance).

Particularly unpleasant list of side effects. 
MD’s write up in the current Private Eye is fairly scathing of the stats used to generate the hype headlines associated with dexamethasone treatment of Covid. 

Not really, the dosage used in the trial was 6mg daily for 10 days. As I wrote previously you may as well try it. The limited evidence is positive and it presents negligible (additional) risk. See https://www.who.int/news-room/q-a-detail/q-a-dexamethasone-and-covid-19

Yes, headlines are hype. It was ever thus.

PS: It was not that the stats were bad. I am sure the statistical analyses would have been conducted appropriately. The issue is with the experimental design, it is very far from a double-blinded RCT, BUT it is a lot better than nothing.

Very few side effects isn’t how I would categorise corticosteroids! More evidence keeps coming out of negative consequences of even low dose short courses. There was that big cohort study in the BMJ from 2017 that showed something like a 5 fold increase risk in sepsis in the month following, 4 fold thrombosis and 2 fold increase fracture risk. There was another study that showed a doubling of the cardiovascular risk for a month following. 
I think you need to differentiate the uses of corticosteroids: symptom relief of non-life threatening conditions like coughs and sinusitis etc should no longer be justified. Then uses to reduce poor outcomes like severe asthma, which are. Then there is the use in severe sepsis to counteract steroid depletion, which probably are, if evidence continues to show more benefit that risk. I’m not informed enough to know if it’s use in COVID is due to this mechanism, but it’s telling that it was only beneficial in the more severe cases.

 
Overall, there seems to be increasing evidence that interrupting our normal inflammatory response is, in most cases, a bad thing: hardly a year seems to go by without another reason to avoid using Non-steroidal anti-inflammatories: ulcer risk, poor bone healing, increased infection risk, increased cardiovascular risk etc.

As I wrote, Dexamethasone is an exceptionally well known drug having been in use for decades.

I wrote that it had few severe side-effects. I clarified that I meant this in the context of the dosage used in the RECOVERY trial.

My remarks were clearly in relation to the use of cortisteroids for the treatment of COVID19 patients as per the recommendation derived from the protocol used in the RECOVERY trial.

I think people fail to understand there are risks either way in use or non-use of any intervention. As the WHO document states, the risk-benefit profile for dexamethasone at this dosage/protocol amongst the recommended cohort is favourable.

So, once again, I posit, for absolute clarity: for the cohort identified by the RECOVERY trial, in the treatment of severe respiratory infections due to COVID19 (and not meeting any of the obvious contras), one may as well try the recommended dosage of dexamethasone.

The previous reply was critical of the RECOVERY trial due to its experimental design. I believe the study to which you refer was in the US (with different prescribing tendencies) and, moreover was a retrospective cohort study - these are always problematic to control for. In the study to which I think you refer they used a self controlled case series design: this introduces its own problems. I do not deny there is evidence, I'm simply trying to put this in similar context.

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