Early guidelines reccommended against corticosteroids in COVID-19 but the NEJM RECOVERY trial showed significant benefit (approx 10% absolute reduction in mortality) when dexamethasone was given to patients receiving either oxygen or mechanical ventilation. However earlier onset of dexamethasone (broadly before O2 requirement) was not effective and possibly harmful.
Here a new cohort study suggests that the earlier the CS tx (AFTER iCU admission) the better. This is not inconsistent with the Recovery trial but there are disconcerting results which I will highlight.
Also, there still are unresolved issues because “ICU admission” is not a disease variable and may very widely from center to center.
The Recovery trial found that CS tx at onset of oxygen administration was superior to broadly administering CS earlier. However O2 treatment is also not a disease variable as O2 may be given for either low SpO2 or shortness of breath.
Yet even low SPO2 or SOB are late markers for inflammation, the severity of which CS are intended to mitigate.
Very early CS (for example at the onset of symptoms) may be detrimental yet waiting for the patient to require O2 is probably too late. What time is optimal? We do not know.
These studies highlight the strengths and weaknesses of using treatments as time markers. As the second study points out it would be ideal if a biomarker could be identified which indicates a need for CS.
The second point is the danger of providing guidelines without sufficient evidence. WHO recommended against CS in COVID pneumonia. They should have said “We dont know”.
The truth is that in critical care guidelines are commonly reversed even when supported by RCT. So why would anyone promulgate “guidelines” based on opinion derived of speculations. We have to learn from this as, given a 10% abs reduction in mort with CS. many lives may have been lost due to the overconfidence of the thought leaders writing guidelines without sufficient evidence support.
This shows how neccessary it is to avoid blindly following guidelines. There is no substitue for investigating the evidence yourself, the lives of your patients may depend on that effort.
In this regard one bothersome finding in the second cited Obs trial was the finding that patients treated with CS prior to ICU had a MUCH higher mortality. This disappeared after adjustment and they argue this may be due to selection of CS unresponders.
Yet, if early CS acts quickly enough to prevent ICU admission in responders then CS are truely amazing in the speed of their effect in COVID. I dont know of any proof for that but it is true that CS have a very rapid effect on conditions causing severe hypoxemia, like cryptogenic organizing pneumonia. If true, prioritized study of optimal timing of CS is absolutely pivotal.
So it is disconcerting that there was about a 10% (absolute) worse mortality in those treated with CS before ICU admission. Until I saw that anomaly these looked to me to be very robust findings.
Are the adjustments made here valid? Any thoughts?