Corticosteroids in the Treatment of Severe CAP
Abstract & Commentary
Commentary by Jerry D. Smilack, MD, FACP, infectious disease consultant at Mayo Clinic Scottsdale in Scottsdale, Arizona
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 six Italian hospitals over a period of nearly three years. All patients had severe community-acquired pneumonia (CAP) (as defined by generally accepted criteria, but see comment below); 34 of the 46 required mechanical ventilation.
The hydrocortisone arm of the study employed a 200-mg initial dose followed by a constant daily infusion of 240 mg during a seven-day period. Most patients received a macrolide, usually in combination with a third- or fourth-generation cephalosporin, fluoroquinolone, antipseudomonal 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 (e.g., 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 the PaO2:FIO2 ratio to greater than 300 (or an increase of >100 compared with entry into the study) and in multiple organ dysfunction syndrome scores, 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.
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.
Commentary
This provocative study by Confalonieri and colleagues 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 one major criterion for the definition of severe pneumonia: presence of a serum creatinine level of 2 mg/dL. This one criterion alone could result in classification of an otherwise ordinary pneumonia as severe pneumonia. The researchers 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 during a similar period, increases survival and reverses shock in patients with pressor-dependent shock.2
The study by Confalonieri and colleagues, 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 CAP should be treated with corticosteroids.
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.
This provocative study by Confalonieri and colleagues adds to accumulating evidence that corticosteroids may have a role in management of critically ill patients.
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