Comparison Between Continuous and Intermittent Administration of Hydrocortisone During Septic Shock: A Randomized Controlled Clinical Trial

Abstract

Objectives: The best modality of administration of hydrocortisone during septic shock has been poorly evaluated and the guidelines remain unclear in this respect. This study aimed to compare bolus of hydrocortisone to a continuous infusion during septic shock. Design: Randomized controlled, open-label trial. Setting: Medical ICU of a university hospital. Patients: Adult patients with septic shock requiring more than 2 mg/h (approximately 33.3 μg/mn) of norepinephrine after adequate fluid administration were eligible. Patients already receiving corticosteroids or who have a contraindication to corticosteroids, patients who died within 24 h and those with a decision of not to resuscitate were excluded. Interventions: Patients were randomized either to receive hydrocortisone 200 mg/d by continuous infusion or by boluses of 50 mg every 6 h throughout the prescription of vasopressors with a maximum of 7 days. Results: Twenty-nine patients were included in each group. Shock reversal was significantly higher in the HC bolus group (66% vs. 35%, P = 0.008). The median time to shock reversal was 5 days (95% CI, 4.31–5.69) in the HC bolus group compared to 6 days (95% CI, 4.80–7.19) in the HC continuous infusion group (log Rank = 0.048). The number of hours spent with blood glucose ≥ 180 mg/dL was higher in the HC continuous infusion group with a median of 64 h [IQR (2–100)] versus 48 h [IQR (14–107)] in the HC bolus group, (P = 0.60), and daily insulin requirements were similar between the two groups (P = 0.63). The occurrence of other side effects, mortality, and ICU LOS were similar between the study groups. Conclusion: Hydrocortisone administered by intermittent bolus was associated with higher shock reversal at day 7 compared with a continuous infusion.

Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model

“…If we use continuous infusion in compliance with the guidelines, the total dose of hydrocortisone administered in the first hour is less than 10 mg, which is an absolutely small dose of steroid in life-threatening, rapidly deteriorating septic shock. In line with this, the intermittent administration of hydrocortisone was better in shock reversal than continuous infusion in a recent clinical study [36]. In this respect, a bolus injection of steroids could be considered.…”

Hyperglycemia risk evaluation of hydrocortisone intermittent boluses versus continuous infusion in septic shock: A prospective randomized trial

“…A recent RCT was conducted on 29 patients by Tilouche et al ., and they found no significant difference between intermittent bolus and continuous infusion; however, the sample size was small, and hyperglycemia was not the primary outcome. [ 17 ] Gibbison et al . conducted a meta-analysis among different regimens of steroids in septic shock patients including hydrocortisone intermittent bolus and continuous infusion; however, they did not find the difference in hyperglycemia between different regimens due to significant variation in defining hyperglycemia between trials.…”

“…[ 13 14 15 ] Tilouche et al . found that hydrocortisone boluses ideal for the faster reversal of shock than continuous infusion,[ 17 ] but their study showed no significant difference in the times until shock reversal between the two groups. Although they did discover a trend toward decreased vasopressor duration in the bolus group by a median of 0.6 days, it was not statistically significant.…”

Circadian Disruption in Critical Illness

“…Two studies assessed whether intermittent vs. continuous administration of hydrocortisone, a corticosteroid, improved reversal of shock in ICU patients. A retrospective study did not show a difference in shock reversal with intermittent vs. continuous administration of hydrocortisone (53), but a small randomized open-label trial showed that intermittent administration of hydrocortisone was associated with improved shock reversal compared to continuous infusion (54). Although it is likely that these protocols affected circadian rhythmicity, this was not measured in either of these studies.…”