Comparison of Hydrocortisone as intermittent bolus or continuous infusion in critically ill patients: A Prospective Randomized Trial

Rationale: In septic shock patients, The Surviving Sepsis Campaign (SSC) Guidelines 2021 have given a weak recommendation based on moderate quality of evidence in favour of using low-dose corticosteroids as an additional therapy in patients who continue to require vasopressor support to maintain hemodynamic stability despite adequate fluid resuscitation. A few recent studies have compared continuous infusion with bolus dose of hydrocortisone for reversal of shock. However, the effect of the two regimes on the reversal of shock remains contradictory.

Aim: To compare intermittent bolus and continuous infusion of Hydrocortisone for septic shock not responsive to fluid and vasopressor therapy

Objectives: To  compare the efficacy of continuous infusion and bolus dose of hydrocortisone on reversal of shock in patients with septic shock in terms of: Shock resolution, Duration of vasopressor therapy, Average daily blood glucose, Average daily insulin requirement, recurrence of new episode of septic shock after 24-hour discontinuation of vasopressors

The study will be conducted in the Department of Anaesthesiology & Critical Care, UCMS and GTB Hospital, Delhi, after obtaining approval from the Institutional Ethics Committee-Human Research. Written and informed consent for participation will be taken from the patients or their next of kin before including them in the study. The study will be registered with ctri.nic.in before enrolling the participants

Study design: Prospective randomized study.

Time frame: April 2024 to August 2025

Inclusion Criteria: Adult patients of either gender admitted in the Intensive Care Units (ICUs) under the Department of Anaesthesiology, UCMS and GTB Hospital, Delhi will be screened for eligibility. Patients, of age >18 years, who fulfill the criteria of Sepsis and Septic Shock as defined by the Third International consensus definitions of Sepsis and Septic Shock and who require norepinephrine

4hr to maintain MAP ≥65 mmHg will be prospectively enrolled in the study.

Exclusion Criteria: Known cases of cardiac dysfunction, Known cases of diabetes before current hospital admission, On steroid therapy before illness, Patients who have received Etomidate during this hospitalization, Patient on vasopressor support for >24 hr before admission to the ICU

Sample Size: Considering shock reversal of 35% with CI of Hydrocortisone versus 66% in the IB group in a study by Tilouche et al, to estimate this difference at α=5% and power = 80%, a sample of 40 patients is required in each group. To account for a 10% loss to follow-up, 44 patients will be included in each group.

Method of Randomization: Patients will be randomly assigned to one of the two intervention groups using a computer-generated random number table. Allocation concealment will be done using sequentially numbered sealed opaque envelopes.

Group IB: Hydrocortisone 200 mg/day as conventional bolus therapy (50-mg IV bolus diluted in 5ml normal saline every 6 hours).

Group CI: Hydrocortisone 200 mg/day as continuous infusion diluted in 50 ml normal saline using a syringe infusion pump.

Blinding: Patients in group IB will receive an infusion of 50 ml of normal saline over 24 hours and those in group CI will receive four bolus injections of 5 ml normal saline IV every 6 hours to ensure the blinding of the observer and patient. The infusions and boluses will be prepared and administered by an anaesthesiologist who is not involved in the study.

Statistical Analysis: Statistical analysis will be done using SPSS v. 20.0 or higher. Qualitative parameters between two groups will be compared using the Chi Square test/Fisher’s Exact Test and within the group, it will be compared by McNemar Test. Quantitative parameters will be compared by Unpaired T-test. Median survival time will be calculated and compared using log-rank test in Kaplan-Meier analysis. A p-value of <0.05 will be taken as significant.