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

Abstract

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 greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 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 (greater than 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 less than 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.

Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis

“…The consensus definition of sepsis as a SIRS that occurs during infection (19) propelled the trialing of different anti-inflammatory approaches ranging from corticosteroids (20) to neutralizing antiendotoxin strategies (21) and from TNFα (3,22) to IL-1 receptor antagonist (23). Unfortunately, none of these treatments resulted in effectively reducing mortality; rather, in some cases, they were detrimental (22).…”

Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

“…Initially, studies performed during the late 1980s and 1990s using high doses of corticosteroids for short periods of time in severe sepsis and septic shock did not improve survival; even more, it increased the risk of dying. [1][2][3][4] More recently, a new concept of "relative" adrenal insuffi ciency in sepsis or critical illness-related corticosteroid insuffi ciency has been coined, and there has been a renewed interest in adrenal function during sepsis. Research studies using smaller doses of corticosteroids for longer period of time (5-7 days) were tested.…”

Insuficiência adrenal na criança com choque séptico

“…2 Later, other studies provided evidence that the use of corticosteroids produced no change to mortality or could even increase it as a result of secondary infections, with the result that it was no longer routinely used. [3][4][5][6] Recently, new work has been published on this group of septic shock patients, some of which has demonstrated better evolution when corticosteroids were used, principally in a group of patients dependent on the use of catecholamines for hemodynamic equilibrium maintenance. [7][8][9][10][11] Recently, a number of different studies have evaluated adrenal gland function in critical patients with sepsis and septic shock, attempting to establish a relationship between adrenal response considered insufficient for the moment with the intensity of hemodynamic alterations and also its repercussion on treatment and evolution.…”