Hydrocortisone for Severe Community- Acquired Pneumonia
Abstract & Commentary
Synopsis: In this multicenter clinical trial of patients with severe community-acquired pneumonia, a 7-day course of low-dose hydrocortisone infusion was associated with decreased signs of inflammation and significant reductions in duration of mechanical ventilation, hospital length of stay, and in-hospital mortality.
Source: Confalonieri M, et al. Am J Respir Crit Care Med. 2005;171:242-248.
Confalonieri and associates report the results of a 6-center Italian clinical trial of hydrocortisone vs placebo in patients hospitalized with severe community-acquired pneumonia (CAP). Patients admitted to the ICUs or respiratory intermediate care units of the participating centers with CAP were considered for the trial. Patients were determined to have severe CAP if they had 2 minor criteria or 1 major criterion from the Table below.
Patients were excluded if they had nosocomial pneumonia, were immunosuppressed, had a life expectancy of less than 3 months because of underlying medical illness, had a recent history of gastrointestinal hemorrhage, or were receiving more than 0.5 mg/kg/day of prednisone. All patients received protocol-guided antibiotic therapy, plus either hydrocortisone (200 mg initially followed by 10 mg/hr for 7 days) or placebo intravenously in a double-blind fashion. Primary end points were improvement in PaO2/FIO2 and multiple organ dysfunction syndrome (MODS) score by day 8; secondary end-points were duration of mechanical ventilation, length of ICU and hospital stays, and survival to hospital discharge.
During the 33 months of the study, 121 patients were evaluated for study entry at the 6 centers and 48 were randomized, of whom 46 (23 in each group) completed the protocol. The patients were mostly male (32/46) and elderly (mean age, 63 years), with admission APACHE II scores of approximately 18. Those randomized to receive hydrocortisone had lower initial PaO2/FIO2 (141 vs 178 mm Hg; P = 0.03), higher admission C-reactive protein levels (55 vs 29 mg/dL; P = 0.04), and more extensive radiographic opacities (chest radiograph score 2.9 vs 2.4; P = 0.03).
Patients randomized to receive hydrocortisone had more rapid improvement in PaO2/FIO2 (P = 0.002), chest radiograph score (P < 0.0001), C-reactive protein levels (P = 0.01), and MODS score (P = 0.003) by day 8. Fewer hydrocortisone-treated patients developed delayed septic shock (0 vs 9; P = 0.001). Patients in the hydrocortisone group requiring ventilatory support (n = 6) spent 4 days on mechanical ventilation (range, 1-27 days) as compared to 10 days (range, 2-44 days) for the 15 patients in the placebo group who were ventilated (P = 0.007). Hospital length of stay was significantly less among patients who received hydrocortisone (P = 0.03). Survival to hospital discharge was 70% in the placebo group and 100% in the hydrocortisone group (P = 0.009).
Comment by David J. Pierson, MD
This study showed that a 7-day course of low-dose intravenous hydrocortisone to patients admitted to the ICU with severe CAP who were managed according to current antibiotic guidelines was associated with more rapid physiologic improvement, shorter duration of ventilatory support, less progression to MODS and septic shock, and better overall survival. Unfortunately, several limitations tend to blunt my enthusiasm for the results. It took 33 months for 6 ICUs to enroll 48 patients with a fairly common condition; the patients in the hydrocortisone and placebo groups differed in initial severity of illness; and allocation to the two groups was uneven at the various participating centers. Patients who received placebo tended to receive invasive mechanical ventilation and those on hydrocortisone were mainly ventilated noninvasively.
The corticosteroid saga continues. High-dose steroids given early in patients with septic shock or acute lung injury appear to be bad, whereas lower-dose steroids given to patients with relative adrenal insufficiency complicating critical illness appear to be good-although identifying which patients those are and knowing when to stop steroids in the patients who do not qualify remain problematic. This study is strongly positive for the use of low-dose hydrocortisone, starting early in hospitalization, in patients with CAP who require ICU admission. Whether subsequent, larger studies will bear out these findings, at this point giving hydrocortisone to patients like those in this study and in the manner used by Confalonieri et al does not appear to be harmful.
David J. Pierson, MD, Pulmonary and Critical Care Medicine Harborview Medical Center University of Washington, is Editor for Critical Care Alert.