Peggy Peck

February 26, 2004

Feb. 26, 2004 (Orlando) — The use of steroids in critically ill patients with sepsis has been both praised and vilified as the debate over efficacy and safety has waxed and waned for more than three decades. Once again, the National Institutes of Health (NIH) is attempting to sort out the evidence with a meta-analysis, which this time comes down on the side of steroid benefit, according to findings reported here at the 33rd Critical Care Congress, the annual meeting of the Society of Critical Care Medicine.

In a meta-analysis published in 1992, NIH researchers reported that steroid use was not beneficial. Now, the latest meta-analysis indicates that steroids are useful but only when started later and delivered in lower doses over a longer period. The analysis also confirmed that a delayed, low-dose five- to seven-day steroid regimen followed by steroid taper for an equal period is effective regardless of response to corticotropin stimulation test.

While the earlier meta-analysis pooled information from nine studies published before 1989, the new analysis includes data from five studies published after 1997, explained Peter C. Minneci, MD, from the critical care medicine department of the NIH in Bethesda, Maryland.

"The studies included in that earlier meta-analysis — eight of which found steroids to be harmful — used protocols that called for high-dose steroid treatment initiated early," Dr. Minneci said. "In recent years there has been renewed interest in steroid replacement in the presence of adrenal insufficiency, so we believed it was time to update the earlier work."

Steroid efficacy in the intensive care unit has been a subject of controversy for "25 to 30 years," J. Christopher Farmer, MD, professor of medicine, pulmonary, and critical care medicine at the Mayo Clinic in Rochester, Minnesota, told Medscape. "You can go back that long and find some big [Veterans Affairs] studies and find some very different doses." Dr. Farmer, who served as cochair of this year's congress, was not involved in the meta-analysis.

The latest analysis is particularly useful because "it illustrates the issue of relative adrenal insufficiency," Dr. Farmer said. "We are looking at what we think is normal cortisol, but it may not be sufficient, so patients may still benefit from steroids."

The difficulty with steroid use is that most published articles provide little evidence to back up claims of efficacy. For example, Dr. Minneci said a literature search identified 1,324 articles, of which 162 were clinical trials, but most of those were not randomized.

"Studies published after 1997 consistently report a beneficial effect for steroids. Four studies report a mortality benefit," Dr. Minneci pointed out.

Analysis indicates several differences in steroid use in the earlier studies compared with the more recent studies. "The newer studies generally enrolled sicker patients — for example, control mortality in the recent studies is 57% while in the earlier studies it was 34%, and 100% of patients in the recent studies are on vasopressors," Dr. Minneci said.

The difference in total steroid dose is also striking: In the earlier studies, total steroid dose was 23,975 mg while in the newer studies total steroid dose is 1,209 mg. "And none of the earlier studies used steroid tapers, while all of newer studies used tapers, Dr. Minneci added.

Moreover, in the studies published before 1989, steroids were initiated in less than two hours, while in the later trials steroid therapy was started at 23 hours and administered for an average of six days rather than one day, which was the case in the earlier studies.

SCCM 33rd Annual Congress: Oral Abstract 77. Presented Feb. 24, 2004.

Reviewed by Gary D. Vogin, MD

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