What is the Right Dose of Corticosteroids?

No matter what reason a patient is in the intensive care unit (ICU) of a hospital every moment and medication they take matters in helping them recover. A recent study looked at what dose of systemic corticosteroids should be given to patients with chronic obstructive pulmonary disease (COPD) exacerbations during their time in critical care.

The study, published in The American Journal of Respiratory and Critical Medicine, noted that exacerbations, particularly those occurring in the ICU, can lead to “sharp declines in the lung function, reductions in activities of daily living, and increased risk of death.”

The authors also noted that in the most extreme ICU exacerbations, patients have been routinely put on a ventilator, which they commented, “are especially concerning, with in-hospital mortality rates of up to 30%.”

As a result of this disturbing trend, the authors noted that corticosteroids have become a viable treatment option for COPD particularly in non-ICU hospital or ambulatory patients. “However, the optimal systemic corticosteroid formulation (e.g., methylprednisolone or prednisone,” dose, route of administration (oral or intravenous), and treatment duration are unclear.”

While the steroids may be a treatment option, the authors believed they carry their own risks, which can be magnified in ICU patients including muscle weakness and hyperglycemia. “These considerations highlight the importance of developing evidence regarding the benefits and risks of systemic corticosteroids for COPD exacerbations treated in ICU populations,” they said.

Even previous studies on the subject have proved inconclusive while citing two earlier works the authors focused on a more recent project where patients at least 40-years-old or older were split into 2 groups with one getting a higher methylprednisolone equivalent dose of >240mg/d, and the second getting a lower dose of less than or equal to 240 methylprednisolone equivalent. In their research the team looked at hospital mortality for the patients as well as secondary outcomes during treatment.

In their results the authors noted that 6% of patients who might have been eligible for treatment during the study were excluded after not being treated with corticosteroids during either of their first 2 days of hospitalization. “In other words, there is very little equipoise about the use of systemic corticosteroids in this population, and clinical trials comparing the use of systemic corticosteroids in this population, and clinical trials comparing the use of systemic corticosteroids versus no systemic corticosteroids are likely to be challenging.”

A second challenge noted by the authors was the fact that 64% of the participants in the pool were given “high-dose,” systemic corticosteroids or an average of 312 mg/d of methylprednisolone while one third received a lower dose of 98 mg/d. The authors said the data was seen to be “suggesting a greater clinical equipoise about the dose of corticosteroids than whether to use it at all.”

Looking at hospital mortality rates the authors found patients in the lower-dose group “had fewer days in the ICU and hospital, shorter length of mechanical ventilation, less frequent use of insulin for hyperglycemia, less frequent fungal infection, and lower hospital costs.”

If the results of the third study are proven in future trials the authors noted the lower-dose and more effective treatment options, “savings in healthcare expenditures could be enormous,” estimating the total value at around $2.5 million for every 1000 patients.

“The study by Kiser and colleagues, together with results of previous studies in non-ICU populations, suggests that more systemic corticosteroids are not better in patients with COPD exacerbations,” the authors said. “From our perspective, continuing with status quo (i.e. widely varying practices regarding the dose of systemic corticosteroids in this population) seems imprudent.

While noting that prior works have shown different results for the higher and lower doses, the authors added, “It is now time to answer the question about what dose of systemic corticosteroids should be used to treat ICU patients with COPD exacerbations.”