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Low-Dose Corticosteroids for Critically Ill Adults With Severe Pulmonary Infections
abstract
This abstract is available on the publisher's site.
Access this abstract nowIMPORTANCE
Severe pulmonary infections, including COVID-19, community-acquired pneumonia, influenza, and Pneumocystis pneumonia, are a leading cause of death among adults worldwide. Pulmonary infections in critically ill patients may cause septic shock, acute respiratory distress syndrome, or both, which are associated with mortality rates ranging between 30% and 50%.
OBSERVATIONS
Corticosteroids mitigate the immune response to infection and improve outcomes for patients with several types of severe pulmonary infections. Low-dose corticosteroids, defined as less than or equal to 400 mg hydrocortisone equivalent daily, can reduce mortality of patients with severe COVID-19, community-acquired pneumonia, and Pneumocystis pneumonia. A randomized clinical trial of 6425 patients hospitalized with COVID-19 who required supplemental oxygen or noninvasive or invasive mechanical ventilation reported that dexamethasone 6 mg daily for 10 days decreased 28-day mortality (23% vs 26%). A meta-analysis that included 7 randomized clinical trials of 1689 patients treated in the intensive care unit for severe bacterial community-acquired pneumonia reported that hydrocortisone equivalent less than or equal to 400 mg daily for 8 days or fewer was associated with lower 30-day mortality compared with placebo (10% vs 16%). In a meta-analysis of 6 randomized clinical trials, low-dose corticosteroids were associated with lower mortality rates compared with placebo for patients with HIV and moderate to severe Pneumocystis pneumonia (13% vs 25%). In a predefined subgroup analysis of a trial of low-dose steroid treatment for septic shock, patients with community-acquired pneumonia randomized to 7 days of intravenous hydrocortisone 50 mg every 6 hours and fludrocortisone 50 μg daily had decreased mortality compared with the placebo group (39% vs 51%). For patients with acute respiratory distress syndrome caused by various conditions, low-dose corticosteroids were associated with decreased in-hospital mortality (34% vs 45%) according to a meta-analysis of 8 studies that included 1091 patients. Adverse effects of low-dose corticosteroids may include hyperglycemia, gastrointestinal bleeding, neuropsychiatric disorders, muscle weakness, hypernatremia, and secondary infections.
CONCLUSIONS AND RELEVANCE
Treatment with low-dose corticosteroids is associated with decreased mortality for patients with severe COVID-19 infection, severe community-acquired bacterial pneumonia, and moderate to severe Pneumocystis pneumonia (for patients with HIV). Low-dose corticosteroids may also benefit critically ill patients with respiratory infections who have septic shock, acute respiratory distress syndrome, or both.
Additional Info
Disclosure statements are available on the authors' profiles:
Low-Dose Corticosteroids for Critically Ill Adults With Severe Pulmonary Infections: A Review
JAMA 2024 Jun 12;[EPub Ahead of Print], R Pirracchio, B Venkatesh, M LegrandFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Corticosteroids for Severe Pulmonary Infections?
Traditionally, we have been told that corticosteroids reduce our immunity, which would lead to the worsening of any bacterial or viral infection. So why then, during the COVID-19 pandemic, did the ICU physicians use corticosteroids for their most severely ill patients?
This paper reviews the literature on mortality reduction with the use of corticosteroids in patients with severe pulmonary infections. The authors looked at severe infections caused by COVID-19, community-acquired pneumonia, influenza, and pneumocystis pneumonia. In all of these cases, the use of low-dose corticosteroids, defined as ≤400 mg of hydrocortisone equivalent daily, resulted in reduced mortality rates.
During the COVID-19 pandemic, we all saw reports on how dexamethasone reduced the mortality rate in patients with the most severe cases of COVID-19. This seems counterintuitive, but it worked. The explanation may be as simple as this: our immune system was overreacting, and the corticosteroid told it to stand down. Think about the SARS-CoV-2 virus. It does not have any weapons or toxins; so, how does it cause so much damage? It is the immune system’s response that is causing the damage.
My simple explanation goes something like this: the SARS-CoV-2 virus enters the cell and starts replicating. Our cells have an auto-destruct mechanism. If the cell detects molecules from a virus or bacterium that is invading, then the cell will self-destruct. The cell does this by sending out a message that calls the army cells to come over and kill it. This self-sacrifice is meant to protect other cells in the body from the infection. These molecules from the infection are called pathogen-associated molecular patterns (PAMPs).
Our cells are also monitored for other kinds of cellular damage. These molecular patterns are called damage-associated molecular patterns (DAMPs). If there is enough damage to the cell, then the cell will also send a message to have itself destroyed. This ensures that damaged cells are eliminated.
Elderly patients experience more damage to their cells owing to their age; hence, they have more DAMPs. Now, if they get COVID-19, then they now have PAMPs as well. This combination of DAMPs and PAMPs would be a very strong signal for the self-destruction process. This is why COVID-19 was so devastating for the elderly.
Now, this process of self-destruction is fine when we are getting rid of just a few lung cells, for example. However, if 10 million lung cells are infected with SARS-CoV-2 and they all send out the message, "Come destroy me," then you can see that this would be an issue. The cytokine message that these cells release is now massive. The army cells will come and destroy the entire neighborhood, and, with so many lung cells destroyed, death is inevitable.
This is where the use of corticosteroids comes in. They can help dampen the immune response and tell the army cells to stand down. This can prevent many lung cells from being destroyed during this cytokine storm. This buys time for the immune system to fight off the infection in a more controlled manner instead of just destroying the entire neighborhood.
So, perhaps, the lesson here is that even a useful process — such as the self-sacrifice of infected cells — still needs to be controlled. When it is allowed to run rampant, it no longer serves a useful purpose and can be detrimental. So, our role as physicians is to help guide and control these processes for the benefit of the patients. In this case, a touch of corticosteroids is exactly what is needed in these patients with severe pulmonary infections.