A Controlled Clinical Trial of High-Dose Methylprednisolone in the Treatment of Severe Sepsis and Septic Shock

• Published in: The New England journal of medicine Vol. 317; no. 11; pp. 653 - 658
• Main Authors: Bone, Roger C, Fisher, Charles J, Clemmer, Terry P, Slotman, Gus J, Metz, Craig A, Balk, Robert A
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 10.09.1987
• Subjects: Adrenal glands; Adult; Aged; Bacterial Infections - drug therapy; Bacterial Infections - mortality; Biological and medical sciences; Blood pressure; Bones, joints and connective tissue. Antiinflammatory agents; Clinical trials; Clinical Trials as Topic; Enrollments; Humans; Medical sciences; Methylprednisolone - administration & dosage; Middle Aged; Mortality; Patients; Pharmacology. Drug treatments; Prospective Studies; Random Allocation; Sepsis; Shock, Septic - drug therapy; Shock, Septic - mortality; United States > US; Shock; Therapeutic efficiency; Human; Intravenous administration; Septicemia; Multicenter study; Mortality; Antiinflammatory agent; Methylprednisolone; Glucocorticoid; Biological activity; Infection; Negative result; Chemotherapy; Bacteriosis; Double blind study; High dose
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198709103171101

The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature >38.3°C [101°F] or <35.6°C [96°F]), tachypnea (>20 breaths per minute), tachycardia (>90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. Three hundred eighty-two patients were enrolled. Treatment — either methylprednisolone sodium succinate (30 mg per kilogram of body weight) or placebo — was given in four infusions, starting within two hours of diagnosis. No significant differences were found in the prevention of shock, the reversal of shock, or overall mortality. In the subgroup of patients with elevated serum creatinine levels (>2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P<0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock. (N Engl J Med 1987; 317:653–8.) SEPSIS can be defined as the systemic response to infection and has been estimated to occur in 70,000 to 300,000 patients in the United States each year. 1 , 2 Hypotension is present in approximately 40 percent of these patients and has been shown to affect survival adversely. 3 4 5 6 7 8 Septic shock has been associated with mortality rates ranging from 40 to 90 percent. 1 , 2 , 4 5 6 , 8 9 10 There is still considerable controversy concerning the use of high doses of corticosteroids in the treatment of severe sepsis or septic shock. 11 12 13 14 15 16 Studies using infusions of endotoxin or live bacteria to produce an injury resembling septic shock in animals have had . . .