Dexamethasone is being called a “Major Breakthrough” based on a recent RCT in the UK. Dexamethasone (Decadron), is an example of a glucocorticoid. Glucocorticoids are sometimes referred to as corticosteroids. Other examples of glucocorticoids include Hydrocortisone, Methylprednisolone, Prednisolone, Prednisone, Betamethasone, and Triamcinolone. Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor in the body. Cortisol (hydrocortisone) is the glucocorticoid we naturally make in our body. It is essential for life, and it regulates or supports various cardiovascular, metabolic, and homeostatic functions. It also plays a big role in our immune system, especially when it comes to reducing certain aspects of inflammation.
This is why we use them all the time in medicine. We sometimes give these steroids for asthma, COPD, rheumatologic type diseases, and countless more diseases. Sometimes we give steroids for meningitis, and also for some forms of cancer. We give them in the early course of severe ARDS, acute respiratory distress syndrome, whether that ARDS is due to infection such as pneumonia, or vaping lung injury, or whatever the cause.
For severe ARDS, we typically give methylprednisone, at a dose of 1 mg/kg per day. So for most people, that ends being around 80 mg per day. This is the equivalent of 15 mg of dexamethasone. The idea here is to suppress the cytokine storm that is taking place, meaning that massive amount of inflammation that causes lung damage and can indirectly cause damage to other organs as well. Our body naturally makes cortisol in our adrenal glands, specifically, in the zona fasciculate of the adrenal cortex. The adrenal gland then secretes cortisol into the bloodstream, and travels to different tissues of the body, and then binds to the glucocorticoid receptor inside cells. It then stimulates the cell to make more anti-inflammatory proteins and reduces the number of pro-inflammatory proteins being made. But giving someone glucocorticoids (steroids) who has an infection is somewhat of a tricky thing because the fear is that if you suppress the body’s immune system, it has the potential to make the infection worse. But sometimes the body’s immune system does more damage than the actual infection. For example, in cases of meningitis that is due to streptococcus or tuberculosis, we give steroids because the medical evidence shows that they have better outcomes when we do so.
Giving someone steroids for viral pneumonia, such as influenza, is more controversial because doing so generally leads to a worse infection. With that said, if the viral pneumonia is so bad to the point of causing severe ARDS, most doctors including myself will give steroids in that situation. This is why the general medical guidelines thus far recommend against giving steroids for COVID pneumonia unless the patient has severe ARDS. We’ve been waiting for RCT to come out for steroids and COVID-19, and here we are now. In March 2020, the RECOVERY (Randomized Evaluation of COVid-19 thERapY) trial was one of that RCT that actually looked at several different potential treatments for COVID-19, which included low-dose dexamethasone (a steroid treatment). This trial was done in the UK and had over 11,500 patients in it.
So this trial has not been peer-reviewed as of the making of this video and has not been published in a journal yet. So everything I know so far is based on what has been released to the general public. In this trial, over 2100 patients were randomized to receive dexamethasone 6 mg once per day for ten days and were compared with over 4300 patients randomized to standard care alone. So 6 mg of dexamethasone is the equivalent of 32 mg of methylprednisolone, so this is about half the dose we would typically use for someone with severe ARDS.
Among the patients who received standard care alone, 28-day mortality was highest in those who required mechanical ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any supplementary oxygen (13%). For patients on ventilators, dexamethasone reduced mortality from 41% to 28%. For patients needing supplemental oxygen, it reduced mortality from 25% to 20%. There was no benefit among those patients who did not require supplemental oxygen. In other words, if someone only has a mild disease, there is no point in giving dexamethasone. Based on these results, 1 death would be prevented by treatment of around 8 ventilated patients, and around 25 patients requiring oxygen alone. So these preliminary results, are significant but do not mean that dexamethasone is a miracle drug. It’s certainly not a cure. But it does seem to help, based on these numbers. And dexamethasone could be of huge benefit in poorer countries with high numbers of Covid-19 patients, because the drug is very cheap, and is widely available.
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