Failure of hydrocortisone to affect outcome in dengue shock syndrome. Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled, double-blind study. Hydrocortisone in the management of dengue shock syndrome. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.
Despite the absence of a clear-cut rationale for their use, corticosteroids are widely employed in the treatment of dengue shock syndrome. Previous comparative therapeutic trials have yielded contradictory results. Resolution of this therapeutic controversy has been attempted with a double-blind evaluation of the clinical effect of steroid administration in dengue shock syndrome. Placebo or a single dose of hydrocortisone hemisuccinate, 50 mg/kg of body weight, was administered randomly to 97 physiologically treated patients with dengue shock syndrome. The severity of disease on admission to the hospital and the effectiveness of treatment were quantified by a World Health Organization scoring system. The response to therapy as measured by mortality, duration of shock, and amount of replacement fluids required was virtually identical in 47 children who were and 50 children who were not treated with steroids. The comparison groups were composed of children similar in age, sex, and severity of illness. It is concluded that hydrocortisone is of no value in the treatment of dengue shock syndrome. Reliance should be placed on appropriate supportive and physiologic therapy. Steroids are widely used in Thailand and other dengue-endemic countries to treat severe dengue shock syndrome. This study was designed to determine whether a single high dose of methylprednisolone will reduce mortality in children with dengue shock syndrome who did not respond to simple fluid and plasma replacement therapy.
                A prospective, randomized, double-blind, controlled trial was conducted in two hospitals in Khon Kaen Thailand during June to September in 1987 and 1988. Sixty-three children with severe dengue shock syndrome were randomized into two groups; the first group received a single dose of methylprednisolone (30 mg/kg) and the second group received placebo.
                There was no significant difference in mortality between the two groups (P = .63). The mortality rate was 12.5% (4/32) in the steroid group and 12.9% (4/31) in the group that received placebo. The sequelae at 2 weeks among treatment and control survivors were not significantly different. These two groups were comparable in age, sex, severity of illness, and duration of shock at the outset of the study. The two treatment groups were similar in subsequent hospital course as determined by maximum and minimum hematocrit level and bleeding severity. The numbers of patients in each group who had liver failure and evidence of disseminated intravascular clotting defect were also comparable. Complications such as occurrence of fever after shock, pneumonia, convulsion, cardiac arrest, pulmonary hemorrhage, and positive hemoculture were not significantly different in the treatment and control groups.
                A single high dose of methylprednisolone does not reduce mortality in severe dengue shock syndrome which does not respond to conventional critical care. A total of 98 patients with dengue shock syndrome admitted into Children's Hospital from February 1973 to February 1974 were randomly selected into 2 groups. A double blind controlled trial of the efficacy of pharmacologic doses of hydrocortisone hemisuccinate was carried out. The 2 groups were confirmed to be completely matched by age, sex and severity of the disease. Nine deaths occurred out of 48 cases in the steroid group (Case Fatality Rate 18.75%) and 22 deaths out of 50 cases in the non-steroid group (Case Fatality Rate 44%), the difference being statistically significant. No significant difference was detected in fluid requirements and other morbidity pattern. Septic shock may be associated with relative adrenal insufficiency. Thus, a replacement therapy of low doses of corticosteroids has been proposed to treat septic shock.
                To assess whether low doses of corticosteroids improve 28-day survival in patients with septic shock and relative adrenal insufficiency.
                Placebo-controlled, randomized, double-blind, parallel-group trial performed in 19 intensive care units in France from October 9, 1995, to February 23, 1999.
                Three hundred adult patients who fulfilled usual criteria for septic shock were enrolled after undergoing a short corticotropin test.
                Patients were randomly assigned to receive either hydrocortisone (50-mg intravenous bolus every 6 hours) and fludrocortisone (50- micro g tablet once daily) (n = 151) or matching placebos (n = 149) for 7 days.
                Twenty-eight-day survival distribution in patients with relative adrenal insufficiency (nonresponders to the corticotropin test).
                One patient from the corticosteroid group was excluded from analyses because of consent withdrawal. There were 229 nonresponders to the corticotropin test (placebo, 115; corticosteroids, 114) and 70 responders to the corticotropin test (placebo, 34; corticosteroids, 36). In nonresponders, there were 73 deaths (63%) in the placebo group and 60 deaths (53%) in the corticosteroid group (hazard ratio, 0.67; 95% confidence interval, 0.47-0.95; P =.02). Vasopressor therapy was withdrawn within 28 days in 46 patients (40%) in the placebo group and in 65 patients (57%) in the corticosteroid group (hazard ratio, 1.91; 95% confidence interval, 1.29-2.84; P =.001). There was no significant difference between groups in responders. Adverse events rates were similar in the 2 groups.
                In our trial, a 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events.
There is insufficient evidence to justify the use of corticosteroids in managing dengue shock syndrome. As corticosteroids can potentially do harm, clinicians should not use them unless they are participating in a randomized controlled trial comparing corticosteroids with placebo.