Comparison of pulse‐dose and high‐dose corticosteroids with no corticosteroid treatment for COVID‐19 pneumonia in the intensive care unit

Abstract

Corticosteroid dosing in the range of 0.5–2 mg/kg/day of methylprednisolone equivalents has become a standard part of the management of intensive care unit (ICU) patients with COVID‐19 pneumonia based on positive results of randomized trials and a meta‐analysis. Alongside such conventional dosing, administration of 1 gm of methylprednisolone daily (pulse dosing) has also been reported in the literature with claims of favorable outcomes. Comparisons between such disparate approaches to corticosteroids for Coronavirus disease 2019 (COVID‐19) pneumonia are lacking. In this retrospective study of patients admitted to the ICU with COVID‐19 pneumonia, we compared patients treated with 0.5–2 mg/kg/day in methylprednisolone equivalents (high‐dose corticosteroids) and patients treated with 1 gm of methylprednisolone (pulse‐dose corticosteroids) to those who did not receive any corticosteroids. The endpoints of interest were hospital mortality, ICU‐free days at Day 28, and complications potentially attributable to corticosteroids. Pulse‐dose corticosteroid therapy was associated with a significant increase in ICU‐free days at Day 28 compared to no receipt: adjusted relative risk (aRR): 1.45 (95% confidence interval [CI]: 1.05–2.02; p = 0.03) and compared with high‐dose corticosteroid administration (p = 0.003). Nonetheless, receipt of high‐dose corticosteroids—but not of pulse‐dose corticosteroids—significantly reduced the odds of hospital mortality compared to no receipt: adjusted Odds ratio (aOR) 0.31 (95% CI: 0.12–0.77; p = 0.01). High‐dose corticosteroids reduced mortality compared to pulse‐dose corticosteroids (p = 0.04). Pulse‐dose corticosteroids—but not high‐dose corticosteroids—significantly increased the odds of acute kidney injury requiring renal replacement therapy compared to no receipt: aOR 3.53 (95% CI: 1.27–9.82; p = 0.02). The odds of this complication were also significantly higher in the pulse‐dose group when compared to the high‐dose group (p = 0.05 for the comparison). In this single‐center study, pulse‐dose corticosteroid therapy for COVID‐19 pneumonia in the ICU was associated with an increase in ICU‐free days but failed to impact hospital mortality, perhaps because of its association with development of severe renal failure. In line with existing trial data, the effect of high‐dose corticosteroids on mortality was favorable.

Pulse versus nonpulse steroid regimens in patients with coronavirus disease 2019: A systematic review and meta‐analysis

“…Subsequently, we excluded 1558 studies because of the following: 1391 studies used inappropriate doses of steroids or lacked the appropriate comparison, 128 studies did not report data regarding the interventions of interest, and 39 studies were excluded due to lack of the appropriate outcomes of interest. Eventually, 10 studies met our inclusion criteria and were included in the meta‐analysis 14–19,22–25 . Figure 1 shows the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) flow chart that illustrates how the final studies were selected.…”

“…Eventually, 10 studies met our inclusion criteria and were included in the meta‐analysis. 14 , 15 , 16 , 17 , 18 , 19 , 22 , 23 , 24 , 25 Figure 1 shows the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) flow chart that illustrates how the final studies were selected.…”

“…Four studies 14,19,23,24 reported the adverse events in the form of superimposed infection or bacterial growth in bodily fluid cultures.…”

“…Quality assessment scoring of the included studies was performed using the NOS for assessing nonrandomized studies, and the scores are summarized in Supporting Information: Table S2. All the included studies [14][15][16][17][18][19][22][23][24][25] were of high quality. There was a visible asymmetry in the funnel plot of the studies that reported mortality, which may suggest the presence of publication bias (Supporting Information: Figure S2).…”

Protocolo Intra-Hospitalar para Abordagem da Doença COVID-19 no Adulto

“…[9][10][11][12][13][14][15] Contudo, nenhum conseguiu demonstrar diminuição da mortalidade em comparação com o esquema de dexametasona recomendado. Em setembro de 2021, Yakoob et al 16 comparou retrospetivamente esquemas de 1 -2 mg/kg/dia de metilprednisolona versus esquemas com 1000 mg/dia versus 0 mg de corticóide, onde foram verificados melhores outcomes nos doentes tratados com doses de 1 -2 mg/kg/dia que nos doentes tratados com doses mais elevadas, onde se verificaram mais complicações associadas ao tratamento. O mesmo se verificou nos restantes estudos com doses superiores a 250 mg/dia de metilprednisolona -sem benefício adicional pelo aumento marcado de complicações.…”