10 Jan 06
Hydrocortisone infusion may improve survival in pneumonia
By Murugan Raghavan and John A Kellum
http://ccforum.com/content/9/6/E24
Hypothesis
Hydrocortisone infusion in severe community-acquired pneumonia (CAP) attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications.
Design
Prospective, randomized, double-blind, placebo-controlled multi-center clinical trial.
Setting
Intensive care units and respiratory intermediate units of six hospitals in Italy between July 2000 and March 2003.
Subjects
Forty-six patients admitted to the intensive care unit with clinical and radiographic evidence of pneumonia and either two minor or one major 1993 American Thoracic Society criterion for severe pneumonia. Patients with nosocomial pneumonia, immunosuppression, acute burn injury, pregnancy, life expectancy less than 3 months, and conditions requiring more than 0.5 mg/kg/day of prednisone equivalent (such as acute asthma and COPD) were excluded.
Intervention
Subjects were randomly assigned to receive hydrocortisone infusion or placebo in addition to protocol guided antimicrobial therapy. Hydrocortisone was given as an intravenous 200 mg bolus followed by infusion at a rate of 10 mg/hour for 7 days.
Outcomes
The primary end-points of the study were improvement in PaO2:FiO2 (PaO2:FiO2 >300 or =100 increase from study entry) and multiple organ dysfunction syndrome (MODS) score by Study Day 8, and development of delayed septic shock. The secondary end-points were duration of mechanical ventilation, length of ICU and hospital stay, and survival to hospital discharge and to 60 days.
Results
The hydrocortisone group had lower PaO2:FiO2, higher chest radiograph score and C-reactive protein (CRP) level at study entry. However by study day 8, treated patients had, compared with control subjects, a significant improvement in PaO2:FiO2 (p = 0.002) and chest radiograph score (p < 0.0001), and a significant reduction in CRP levels (p = 0.01), MODS score (p = 0.003), and delayed septic shock (p = 0.001). Hydrocortisone treatment was associated with a significant reduction in length of hospital stay (p = 0.03) and mortality (p = 0.009). There were seven deaths in the control group, whereas none in the hydrocortisone group.
Conclusion
A seven-day course of low-dose hydrocortisone infusion in patients with severe community-acquired pneumonia was associated with a significant reduction in duration of mechanical ventilation, hospital length of stay, and hospital mortality.