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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 200 mg group | Active Comparator | 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. |
|
| 300 mg group | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydrocortisone hemisuccinate | Drug | 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. |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gilles Bernardin, M.D. | Association Niçoise de Réanimation Médicale | Principal Investigator |
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The data are available for additional analysis
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| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
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| ID | Term |
|---|---|
| C007133 | hydrocortisone hemisuccinate |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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|
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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 |
| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |