Corticosteroid Response in Septic Shock Predicted by Transcriptomic Profiles

By | December 5, 2018

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Patients with the SRS2 phenotype who received hydrocortisone experienced an increase in mortality.
Patients with the SRS2 phenotype who received hydrocortisone experienced an increase in mortality.

Transcriptomic sepsis response signatures (SRS) may be helpful to identify patient response to corticosteroids at the onset of septic shock, according to a post hoc analysis of the VANISH trial (Vasopressin vs Noradrenaline as Initial Therapy in Septic Shock; ISRCTN Clinical Trial Identifier: 20769191) published in the American Journal of Respiratory and Critical Care Medicine.

Patients with septic shock who required vasopressors were enrolled in the study within a 6-hour period of shock onset (N=176), all of whom were characterized by one of two transcriptomic SRS: SRS1 (ie, immunocompromised; n=83) or SRS2 (ie, immunocompetent; n=93). Investigators randomly assigned patients to receive either an infusion of norepinephrine or vasopressin followed by hydrocortisone or placebo after the maximum infusion rate of norepinephrine or vasopressin was reached.

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A total of 27 and 35 patients categorized as SRS1 received hydrocortisone and placebo, respectively. In patients categorized as SRS2, a total of 31 and 24 patients received hydrocortisone and placebo, respectively. Researchers performed genome-wide gene expression profiling in all participants.

In terms of the effect of vasopressor vs norepinephrine on 28-day mortality, no differences were found between patients in the SRS1 group (odds ratio [OR], 1.50; 95% CI, 0.58-3.88) and patients in SRS2 group (OR, 0.94; 95% CI, 0.36-2.46; interaction P =.50). A significant interaction between treatment and SRS endotype, however, was noted in patients who received either hydrocortisone or placebo (hydrocortisone vs placebo in SRS1 patients: OR, 0.85; 95% CI, 0.30-2.43 and SRS2: OR, 7.9; 95% CI, 1.6-39.9; interaction P =.02).

In addition, the researchers observed an increase in mortality in patients with the SRS2 phenotype who received hydrocortisone (OR, 7.9; 95% CI, 1.6-39.9). With regard to the rates of serious adverse events, no differences were found between the SRS1 (7%) and SRS2 (6%) phenotypes (P =.84).

The post hoc design of the analysis, the small number of participants and the short window for study recruitment represented potential limitations of this study.

“Although further work is required to validate these findings and to better understand the utility of endotype assignment based on transcriptomic profiles in sepsis, our findings suggest that SRS endotypes should be used in future biomarker guided trials of corticosteroids in septic shock,” the researchers concluded.

Reference

Antcliffe DB, Burnham KL, Al-Beidh F, et al. Transcriptomic signatures in sepsis and a differential response to steroids: from the VANISH randomized trial [published online October 26, 2018]. Am J Respir Crit Care Med. doi:10.1164/rccm.201807-1419OC

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