Is Pulsed Steroid Riskier For COVID-19?

SAN FRANCISCO — For hospitalized COVID-19 patients, pulsed methylprednisolone was not a good alternative to dexamethasone, based on poorer outcomes observed with it in a large Japanese study.

Among 1,197 patient pairs with a matched propensity, those who received high-dose IV methylprednisolone pulses were 42% relatively more likely to die before discharge than those who received standard of care IV dexamethasone (12.0% vs. 8.8%, OR 1.42, 95% CI 1.09-1.85), reported Atsuyuki Watanabe, MD, of the University of Tsukuba Hospital in Japan, at the Critical Care Congress of the Society of Critical Care Medicine.

Hyperglycemia was also more common in the pulsed methylprednisolone group (16.3% vs. 9.7%, OR 1.81, 95% CI 1.42-2.32), and hospital stay was a median 1 day longer (13 vs 12, P=0.002).

“Providers should be aware of the potential benefits and risks of the type and dose of corticosteroids,” Watanabe said.

Dexamethasone was the first drug shown to reduce mortality from severe COVID-19, with a 35% relative reduction in deaths in the RECOVERY study. However, it was only effective in patients on mechanical ventilation or oxygen, not those not requiring respiratory support, and a high dose was associated with an increased risk of mortality. A Veterans Affairs study also confirmed no benefit and potential harm from dexamethasone in hospitalized COVID-19 patients receiving room air or oxygen with nasal cannulas.

In the study by Watanabe and colleagues, no difference was seen in the subgroup of 171 patients with severe COVID-19 who were directly mechanically ventilated on the day or the day after admission. However, pulsed methylprednisolone had a significant disadvantage for all interventions in those not on mechanical ventilation, with the addition of a more than double rate of fungal infections (5.3% vs. 2.1%, P<0.001).

These results were not surprising given the previous RECOVERY and VA results, commented Amy Dzierba, PharmD, SCCM Congress Co-Chair, of New York-Presbyterian Hospital/Columbia Irving Medical Center in New York City.

“It made sense that there was no difference in patients who were on mechanical ventilation — they were the ones who benefited from the steroids regardless of dose or drug,” she said MedPage today“While people who are less ill do not require mechanical ventilation…they benefit from the lower dose of steroids compared to the higher dose, perhaps because side effects may have overshadowed any benefit.”

Methylprednisolone is recommended for acute respiratory distress syndrome (ARDS), but “the effect of its high-dose therapy on COVID-19 has not been clearly established,” Watanabe noted.

He pointed to previous studies linking methylprednisolone to better biomarker measures. And a pilot study of 68 patients showed better clinical improvement and numerically higher survival rates with pulsed methylprednisolone in hospitalized patients with severe COVID-19.

However, in a small Greek observational study, 3-day pulses of methylprednisolone had shown an 89% greater risk of death in intubated patients, while non-intubated patients had a much shorter length of hospital stay and a trend toward earlier extubation. A single-center US study showed no effect on mortality but more renal failure with pulsed methylprednisolone in hospitalized COVID-19 patients.

The worse outcomes in the Japanese cohort using pulsed methylprednisolone could be attributed to increased adverse events with high-dose steroids, Watanabe suggested.

However, he warned of the potential for unmeasured mix-ups, as well as the lack of data on laboratory measurements or ventilator settings. He also warned that the observational study could not establish causality.

The study included adults in an inpatient claims database who were hospitalized for COVID-19 at more than 350 acute care hospitals in Japan. They received either pulsed methylprednisolone (250 mg/day or more) or intravenous dexamethasone on the day of admission or the day after. Patients were matched for patient characteristics, comorbidities at baseline, hospital stays, treatments received on the day or day after admission, and hospital size.

Of the study population, 30% were female, 58% had diabetes, 35% had hypertension, and 13% had obesity. The average age was 62 years. Among them, 17% of the patients were in the ICU, 15% received mechanical ventilation, and 1% received extracorporeal membrane oxygenation (ECMO).


Watanabe and co-authors and Dzierba disclosed no industry affiliations.

Main source

Society for Intensive Care Medicine

Credit: Watanabe A, et al. “Pulse methylprednisolone versus dexamethasone in COVID-19: A multicenter cohort study” SCCM 2023.

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