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Hydrocortisone Fails to Make a Dent in Septic Shock Deaths

— But does chip away at need for blood transfusion, ADRENAL trial shows

MedpageToday

Glucocorticoid therapy made no difference in the risk of mortality for mechanically-ventilated patients in septic shock, the ADRENAL trial reported.

At 90 days, mortality reached 27.9% of those randomized to a continuous infusion of hydrocortisone (200 mg daily for 7 days) and 28.8% of peers getting a placebo (OR 0.95, 95% CI 0.82-1.10). The lack of difference was observed across prespecified subgroups, according to a group led by Balasubramanian Venkatesh, MD, of Australia's Wesley Hospital.

Findings from their ADRENAL trial were presented at the Critical Care Reviews meeting in Belfast, Ireland, and published simultaneously online in the .

"Biting my nails" was how Paul Marik, MD, of Eastern Virginia ľֱ School in Norfolk, described his anticipation for the trial, telling ľֱ that he found results "credible and believable.

"I think this will theoretically change people's approach," said Marik, who was not involved with the trial. "This has been a controversial issue for maybe 20 years, and I think this is the definitive study which shows that corticosteroids alone do not change outcomes. What this does now is there is no justification to use steroids alone. I think this is a big study, it's well-designed."

Nonetheless, he said he is holding out for the possibility that steroids and vitamin C together will do the trick to improve survival. There are a few studies testing this that may come out in 2019 or 2020.

In ADRENAL, 3,800 patients with septic shock getting mechanical ventilation were randomized at 69 sites across Australia, the U.K., New Zealand, Saudi Arabia, and Denmark. Hydrocortisone and placebo recipients shared similar baseline characteristics.

The initial episode of mechanical ventilation did not last as long with hydrocortisone (median 6 versus 7 days, HR 1.13, 95% CI 1.05-1.22). On the whole, however, recurring episodes of ventilation neutralized this benefit in terms of number of days alive and free from mechanical ventilation (61.2 versus 59.1, P=NS).

Glucocorticoid therapy was associated with more adverse events (1.1% versus 0.3%, P=0.009).

However, recipients had a faster resolution of shock (median 3 versus 4 days, HR 1.32, 95% CI 1.23-1.41) and were less likely to receive a blood transfusion (37.0% versus 41.7%, OR 0.82, 95% CI 0.72-0.94).

Venkatesh and colleagues highlighted the latter result, calling it "hypothesis-generating."

When it came to other endpoints, there was no difference between groups in mortality at 28 days, rate of recurrent shock, number of days alive and out of the ICU or hospital, recurrence of mechanical ventilation, rate of renal-replacement therapy, or incidence of new-onset bacteremia or fungemia.

It was possible, however, that other secondary infections occurred, since the authors only collected data on bacteremia and fungemia. In addition, they did not assess long-term neuromuscular weakness and lacked adjudication for adverse events.

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    Nicole Lou is a reporter for ľֱ, where she covers cardiology news and other developments in medicine.

Disclosures

Venkatesh reported grants from the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand.

Marik and Levy disclosed no relevant conflicts of interest.

Primary Source

New England Journal of Medicine

Venkatesh B, et al "Adjunctive glucocorticoid therapy in patients with septic shock" New Engl J Med 2018; DOI: 10.1056/NEJMoa170835