Corticosteroids in the Treatment of Severe Community-Acquired Pneumonia

Abstract and Commentary

Synopsis: Hydrocortisone administration to patients with severe community-acquired pneumonia was associated with improved oxygenation, radiographic clearing, hospital length-of-stay, and patient survival.

Source: Confalonieri M, et al. Hydrocortisone Infusion For Severe Community-Acquired Pneumonia: A Preliminary Randomized Study. Am J Respir Crit Care Med. 2005;171:242-248.

Forty-six patients were entered into a prospective randomized, double-blind, placebo-controlled trial conducted at 6 Italian hospitals over a nearly 3-year period. All patients had severe community-acquired pneumonia (as defined by generally accepted criteria, but see comment below); 34 of the 46 required mechanical ventilation. The hydrocortisone a3rm of the study employed a 200-mg initial dose followed by a constant daily infusion of 240 mg over a 7-day period. Most patients received a macrolide, usually in combination with a third- or fourth-generation cephalosporin, fluoroquinolone, anti-pseudomonal penicillin, or aminoglycoside. Antimicrobials were modified in slightly more than half of the patients either because of the patients’ failure to improve or because of identification of specific pathogens (such as Staphylococcus aureus or legionella).

At study entry, patients randomized to receive hydrocortisone were sicker, as reflected in lower PaO2:FIO2 ratios (141 vs 178) and more extensive radiographic involvement. Primary end points of the study were improvement in PaO2:FIO2 ratio to greater than 300 (or an increase of >100 compared with entry into the study) and in multiple organ dysfunction syndrome score, as well as development of delayed septic shock (not specifically defined in the study). Secondary end points included duration of mechanical ventilation, length of intensive care unit and hospital stay, and survival.

Confalonieri and colleagues reported that significant benefit was found in hydrocortisone-treated patients. Oxygenation (measured by the PaO2:FIO2 ratio) improved significantly in 87% (compared with 39% of placebo recipients), as did the chest radiograph (91% vs 22%, steroid vs placebo), C-reactive protein levels, multiple organ dysfunction score, need for mechanical ventilation (26% vs 65%), and appearance of delayed shock (0% vs 43%). Intensive care unit and overall hospital length-of-stay was shortened, and survival-to-hospital discharge increased (see Figure 1).

Although not statistically significant, adult respiratory distress syndrome, nosocomial infection, acute renal failure, and other complications occurred more frequently in the placebo group. No side effects appeared to be related to hydrocortisone therapy.

Comment by Jerry D. Smilack, MD, FACP

This provocative study by Confalonieri et al adds to accumulating evidence that corticosteroids may have a role in management of critically ill patients. The design and conduct of the study were well conceived and executed, although I might quibble somewhat with inclusion of 1 major criterion for the definition of severe pneumonia: presence of a serum creatinine of 2 mg/dL. This 1 criterion alone could result in classification of an otherwise ordinary pneumonia as severe pneumonia. Confalonieri et al do not indicate how many patients were classified as such solely as a result of this definitional oddity.

Annane and colleagues’ seminal study of the use of hydrocortisone and fludrocortisone in patients with septic shock clearly demonstrated a salutary effect of these agents, particularly in the subset with relative adrenal insufficiency.1 A recent meta-analysis concluded that low-dose hydrocortisone, when given for 5 to 7 days and then tapered over a similar period, increases survival and reverses shock in patients with pressor-dependent shock.2

The study by Confalonieri et al, although quite impressive, enrolled only 46 patients. It will be critical to see confirmation of their findings by other investigators studying larger numbers of patients, before concluding that all patients with severe community-acquired pneumonia should be treated with corticosteroids.

Dr. Smilack, Infectious Disease Consultant, Mayo Clinic Scottsdale, Scottsdale, AZ, is Associate Editor of Infectious Disease Alert.

References

1. Annane D, et al. Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock. JAMA. 2002;288:862-871.

2. Minneci PC, et al. Meta-Analysis: The Effect of Steroids on Survival and Shock During Sepsis Depends on the Dose. Ann Intern Med. 2004;141: 47-56.