Authors: Matthew Huebner, Julie Willmon, Kevin Pacheco
Background
Septic shock is a life-threatening condition characterized by a dysregulated host response to an infection. Hydrocortisone and fludrocortisone are corticosteroids that are proposed to modulate the host response and may improve outcomes in septic shock. In the ADRENAL trial, hydrocortisone did not lower mortality versus placebo1, whereas the APROCCHSS trial demonstrated a mortality benefit with the combination of hydrocortisone plus fludrocortisone2. Evidence from clinical trials is conflicting, and there is a gap in trial data comparing the combination to hydrocortisone monotherapy. However, guidelines suggest the use of both hydrocortisone and fludrocortisone for critically ill patients with septic shock3. The objective of this study is to assess clinical outcomes associated with the current prescribing practices of corticosteroids in septic shock at AdventHealth Central Florida Division hospitals.
Methods
A retrospective analysis was conducted in critically ill patients with septic shock to evaluate the effect of hydrocortisone versus hydrocortisone plus fludrocortisone. The primary outcome was the number of vasopressor free days (VFD) out of 28. Secondary outcomes included dose of norepinephrine upon initiation of corticosteroids, number of vasopressors, days of vasopressors, hours of vasopressors, need for mechanical ventilation, duration of mechanical ventilation, recurrence of shock, in hospital mortality, and time to discharge from ICU and hospital. Safety outcomes included new onset infections, number of days with blood glucose >180 g/dL, and number of days with serum sodium out of normal range.
Results
From the 140 patients included in this analysis, the median vasopressor free days out of 28 was 0 days (IQR 0-24) in the hydrocortisone group versus 0 days (IQR 0-24) in the hydrocortisone plus fludrocortisone group (P=0.59). When vasopressor free days are adjusted for hospice related deaths, the median VFD was 21.5 days (IQR 0-25) in the hydrocortisone group versus 19 days (IQR 0-24) in the hydrocortisone plus fludrocortisone group (P=0.32). The days of vasopressors were significantly higher in the hydrocortisone plus fludrocortisone group (5 vs 3 days, P=0.005) and hours of norepinephrine (83.0 vs 52.4 hours, P=0.008), vasopressin (51.2 vs 35.6 hours, P=0.04), phenylephrine (83.2 vs 18.3 hours, P=0.03) but not epinephrine (43.8 vs 27.2 hours, P=0.21) compared to the hydrocortisone group. Secondary outcomes for each group were similar, which included the dose of norepinephrine when corticosteroids were initiated in the hydrocortisone plus fludrocortisone group compared to hydrocortisone alone (0.2 vs 0.3 mcg/kg/min, P=0.34), number of vasopressors (2 vs 2 vasopressors, P=0.38), mechanical ventilation (63.9% vs 78.6%, P=0.09), duration of mechanical ventilation (4 vs 3 days, P=0.76), recurrence of shock (15.7% vs 15.7%, P=1.0), in hospital mortality (34.3 vs 37.1%, P=0.72), time to ICU discharge (6 vs 6 days, P=0.19), and time to hospital discharge (11 vs 10 days, P=0.55). The safety outcomes were also similar among both groups, which included new onset infections in the hydrocortisone plus fludrocortisone group compared to hydrocortisone alone (5.7% vs 5.7%, P=1.0), median number of days with BG>180 g/dL (1.5 vs 2 days, P=0.14), and median number of days with sodium out of normal range (1 vs 1 day, P=0.65).
Conclusion
Among critically ill patients with septic shock, the number of vasopressor free days did not significantly differ between the hydrocortisone plus fludrocortisone and hydrocortisone monotherapy groups. However, the days of vasopressor use was higher in the group containing fludrocortisone.
