Hydrocortisone therapy for patients with multiple trauma: the randomized controlled HYPOLYTE study.

Abstract

CONTEXT:

The role of stress-dose hydrocortisone in the management of trauma patients is currently unknown.

OBJECTIVE:

To test the efficacy of hydrocortisone therapy in trauma patients.

DESIGN, SETTING, AND PATIENTS:

Multicenter, randomized, double-blind, placebo-controlled HYPOLYTE (Hydrocortisone Polytraumatise) study. From November 2006 to August 2009, 150 patients with severe trauma were included in 7 intensive care units in France.

INTERVENTION:

Patients were randomly assigned to a continuous intravenous infusion of either hydrocortisone (200 mg/d for 5 days, followed by 100 mg on day 6 and 50 mg on day 7) or placebo. The treatment was stopped if patients had an appropriate adrenal response.

MAIN OUTCOME MEASURE:

Hospital-acquired pneumonia within 28 days. Secondary outcomes included the duration of mechanical ventilation, hyponatremia, and death.

RESULTS:

One patient withdrew consent. An intention-to-treat (ITT) analysis included the 149 patients, a modified ITT analysis included 113 patients with corticosteroid insufficiency. In the ITT analysis, 26 of 73 patients (35.6%) treated with hydrocortisone and 39 of 76 patients (51.3%) receiving placebo developed hospital-acquired pneumonia by day 28 (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.30-0.83; P = .007). In the modified ITT analysis, 20 of 56 patients (35.7%) in the hydrocortisone group and 31 of 57 patients (54.4%) in the placebo group developed hospital-acquired pneumonia by day 28 (HR, 0.47; 95% CI, 0.25-0.86; P = .01). Mechanical ventilation-free days increased with hydrocortisone by 4 days (95% CI, 2-7; P = .001) in the ITT analysis and 6 days (95% CI, 2-11; P < .001) in the modified ITT analysis. Hyponatremia was observed in 7 of 76 (9.2%) in the placebo group vs none in the hydrocortisone group (absolute difference, -9%; 95% CI, -16% to -3%; P = .01). Four of 76 patients (5.3%) in the placebo group and 6 of 73 (8.2%) in the hydrocortisone group died (absolute difference, 3%; 95% CI, -5% to 11%; P = .44).

CONCLUSION:

In intubated trauma patients, the use of an intravenous stress-dose of hydrocortisone, compared with placebo, resulted in a decreased risk of hospital-acquired pneumonia.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00563303.

• Authors: Antoine Roquilly, Pierre Joachim Mahe, Philippe Seguin, Christophe Guitton, Hervé Floch, Anne Charlotte Tellier, Laurent Merson, Benoît Renard, Yannick Malledant, Laurent Flet, Véronique Sebille, Christelle Volteau, Damien Masson, Jean Michel Nguyen, Corinne Lejus, Karim Asehnoune
• Journal: JAMA (JAMA) Vol. 305 Issue 12 Pg. 1201-9 (Mar 23 2011) ISSN: 1538-3598 [Electronic] United States
• PMID: 21427372 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Hydrocortisone

Topics

• Adolescent
• Adrenal Insufficiency (diagnosis, drug therapy, etiology)
• Adult
• Anti-Inflammatory Agents (therapeutic use)
• Cross Infection (etiology, prevention & control)
• Double-Blind Method
• Female
• Humans
• Hydrocortisone (therapeutic use)
• Infusions, Intravenous
• Intensive Care Units
• Intubation, Intratracheal
• Male
• Middle Aged
• Multiple Trauma (complications)
• Pneumonia (etiology, prevention & control)
• Respiration, Artificial
• Young Adult