Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study

Abstract

Purpose Although there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19. Methods Multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs. The primary outcome was 90-day mortality. Subsequent analyses in clinically relevant subgroups by age, ICU baseline illness severity, organ damage, laboratory findings and mechanical ventilation were performed. High doses of corticosteroids (≥ 12 mg/day equivalent dexamethasone dose), early administration of corticosteroid treatment (< 7 days since symptom onset) and long term of corticosteroids (≥ 10 days) were also investigated. Results Between February 2020 and October 2021, 4226 patients were included. Of these, 3592 (85%) patients had received systemic corticosteroids during hospitalisation. In the propensity-adjusted multivariable analysis, the use of corticosteroids was protective for 90-day mortality in the overall population (HR 0.77 [0.65–0.92], p = 0.003) and in-hospital mortality (SHR 0.70 [0.58–0.84], p < 0.001). Significant effect modification was found after adjustment for covariates using propensity score for age ( p = 0.001 interaction term), Sequential Organ Failure Assessment (SOFA) score ( p = 0.014 interaction term), and mechanical ventilation ( p = 0.001 interaction term). We observed a beneficial effect of corticosteroids on 90-day mortality in various patient subgroups, including those patients aged ≥ 60 years; those with higher baseline severity; and those receiving invasive mechanical ventilation at ICU admission. Early administration was associated with a higher risk of 90-day mortality in the overall population (HR 1.32 [1.14–1.53], p < 0.001). Long-term use was associated with a lower risk of 90-day mortality in the overall population (HR 0.71 [0.61–0.82], p < 0.001). No effect was found regarding the dosage of corticosteroids. Moreover, the use of corticosteroids was associated with an increased risk of nosocomial bacterial pneumonia and hyperglycaemia. Conclusion Corticosteroid in ICU-admitted patients with COVID-19 may be administered based on age, severity, baseline inflammation, and invasive mechanical ventilation. Early administration since symptom onset may prove harmful. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-022-06726-w.

Renaissance of glucocorticoids in critical care in the era of COVID-19: ten urging questions

“…Another recently published study demonstrated that mortality rose in patients ≥ 80 years [ 35 ]. A recent large multicenter observational study in the ICU-admitted patients found a survival benefit in patients > 60 years [ 36 ]. The timing of GCs prescription is another valid question: an early administration represents other clinical scenarios that could modulate the benefits conferred by GCs.…”

“…The timing of GCs prescription is another valid question: an early administration represents other clinical scenarios that could modulate the benefits conferred by GCs. Remarkably, in the CIBERESUCICOVID study [ 36 ], it was revealed that GCs increased mortality in the ICU-admitted patients when the therapy was initiated < 7 days of symptoms onset. Regarding early GC administration in ICU patients, the results are controversial; an early administration seemed beneficial [ 37 ] but patients receiving GCs with a 48 h delay were not discarded [ 36 ].…”

“…Remarkably, in the CIBERESUCICOVID study [ 36 ], it was revealed that GCs increased mortality in the ICU-admitted patients when the therapy was initiated < 7 days of symptoms onset. Regarding early GC administration in ICU patients, the results are controversial; an early administration seemed beneficial [ 37 ] but patients receiving GCs with a 48 h delay were not discarded [ 36 ]. It remains unclear what the most efficient doses are in specific clinical situations.…”

“…It remains unclear what the most efficient doses are in specific clinical situations. It was clearly demonstrated that in COVID-19, 12 mg of dexamethasone was not more efficient (versus 6 mg), leading to the recommendation of the low dosage [ 36 ]. Duration of GC treatment also remains an open question.…”

“…The results of a recent meta-analysis showed that treatment for more than 7 days improved survival compared to shorter treatments [ 38 ]. The GC treatment in the ICU patients for more than 10 days was associated with a higher reduction in 90-day mortality [ 36 ]. The clinical characteristics associated with the efficacy of GCs are summarized in Fig.…”