Hydrocortisone 50 mg Every 6 Hours Compared to Hydrocortisone 300 mg Per Day in Treatment of Septic Shock.

Study Overview
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Brief Summary
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We performed a multicenter, prospective, randomized, double-blind, pilot study in four adult medical intensive care units. Patients presenting septic shock were rapidly administered one of two regimens of hydrocortisone, either a 50-mg intravenous bolus every six hours during seven days (200-mg group) or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for five days (300-mg group). Hydrocortisone was stopped abruptly at the end of treatment.

Detailed Description
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Hydrocortisone hemisuccinate (Hydrocortisone Upjohn) was supplied as a powder in 100 mg vials to be reconstituted with 2 ml of sterile water diluent. The placebo was saline serum supplied as 10 ml ampoules. The study drugs were administered according to two protocols. In the 200-mg group, patients received an intravenous bolus of 50 mg of hydrocortisone every six hours for seven days associated with a continuous infusion of placebo for five days. In the 300-mg group, patients received an initial bolus of 100 mg of hydrocortisone followed by a continuous infusion of 300 mg per day for five days associated with a bolus of placebo every six hours for seven days. In the two groups, hydrocortisone was stopped abruptly at the end of treatment. The investigators had the choice or resuming hydrocortisone at the end of the fifth day if deemed necessary.

Official Title
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Double Blinded, Randomized Trial, Comparing Intravenous Bolus of 50 mg of Hydrocortisone Every 6 Hours for 7 Days With a Continuous Infusion of 300 mg Per Day of Hydrocortisone 300-mg Group During 5 Days in the Treatment of Septic Shock.

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: Hydrocortisone hemisuccinate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients over 18 years old septic shock in accordance with the American College of Chest Physicians/Society of Critical Care Medicine Consensus Committee criteria. Septic shock was managed in accordance with the 2004 edition of the Surviving Sepsis Campaign guidelines. no minimal vasopressor dose was needed to enter the trial. Exclusion Criteria: medical history of adrenal insufficiency ongoing corticosteroid treatment pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 200 mg group<br>Patients received an intravenous bolus of 50 mg of hydrocortisone every six hours for seven days associated with a continuous infusion of placebo for five days. | Drug: Hydrocortisone hemisuccinate<br>* In the 200-mg group, patients received an intravenous bolus of 50 mg of hydrocortisone every six hours for seven days associated with a continuous infusion of placebo for five days. In the 300-mg group, patients received an initial bolus of 100 mg of hydrocortisone followed by a continuous infusion of 300 mg per day for five days associated with a bolus of placebo every six hours for seven days.<br>* Other names: Saline solution as placebo;|
| Experimental: 300 mg group<br>Patients received an initial bolus of 100 mg of hydrocortisone followed by a continuous infusion of 300 mg per day for five days associated with a bolus of placebo every six hours for seven days. | Drug: Hydrocortisone hemisuccinate<br>* In the 200-mg group, patients received an intravenous bolus of 50 mg of hydrocortisone every six hours for seven days associated with a continuous infusion of placebo for five days. In the 300-mg group, patients received an initial bolus of 100 mg of hydrocortisone followed by a continuous infusion of 300 mg per day for five days associated with a bolus of placebo every six hours for seven days.<br>* Other names: Saline solution as placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | The primary end point was to determine a difference in 28-day mortality between the 200-mg and 300-mg groups. | 28-day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of permanent shock between groups | Permanent shock (PS) was defined as permanent catecholamine support (epinephrine or norepinephrine) in the ICU, from the onset of septic shock to death without a period of reversal. | 28-day | 
| Incidence of shock relapse between groups | Shock relapse (SR) was defined as recurrence of septic shock requiring catecholamine resumption. | 28-day | 
| Incidence of post hydrocortisone hemodynamic rebound between groups | Post hydrocortisone hemodynamic rebound (PHHR) was defined as SR within 48 hours after hydrocortisone cessation. | 28-day | 
| Incidence of adverse events between groups. | Incidences of hemorrhagic events, superinfections and the amount of needed insulin were compared between the two groups. | 28-day |