Rationale:

• Drugs that have not been shown to be beneficial in clinical studies should not be used purely on theoretical grounds.
• Studies showed that a single high dose of methylprednisolone did not reduce mortality in patients with severe dengue shock syndrome.
• Carbazochrome sodium sulfonate does not prevent dengue vascular permeability or shock in humans.
• There are only a few case reports on the potential use of high-dose immunoglobulins, desmopressin, or recombinant activated factor VII in patients with dengue infections.

Evidence:

• In a prospective, double-blind, randomized, controlled trial conducted in two hospitals in Thailand in 1987 and 1988, 63 children with severe dengue shock syndrome were randomly assigned to either a single dose of methylprednisolone, 30 mg/kg, or placebo. No significant difference in mortality was found between the two groups (P=0.63). The mortality rate was 12.5% (4 of 32 patients) in the group that received methylprednisolone and 12.9% (4 of 31 patients) in the group that received placebo. Sequelae at 2 weeks among the survivors were not significantly different between groups. Subsequent hospital course, as determined by maximum and minimum hematocrit, and bleeding severity were similar between groups. The numbers of patients in each group who had liver failure and evidence of disseminated intravascular clotting defect were comparable. Complications, such as occurrence of fever after shock, pneumonia, convulsions, cardiac arrest, pulmonary hemorrhage, and positive hemoculture result, were not significantly different between groups (109).
• A randomized, placebo-controlled trial included 95 children with dengue hemorrhagic fever/dengue shock syndrome in two hospitals during 1992. Carbazochrome sodium sulfonate (n=45) or B vitamins as placebo (n=50) were given as a bolus infusion and then as a continuous drip for 24 hours; 300 mg of carbazochrome sodium sulfonate was administered on the first 2 days, and 150 mg was given on the third day. No significant difference in shock or pleural effusion was noted between the two groups. Shock developed in 4 patients (8.9%) in the carbazochrome sodium sulfonate group and in 3 patients (6%) in the placebo group (P=0.44). Pleural effusion was found at 0, 24, 48, and 72 hours after admission in 4.4%, 20%, 31.1%, and 20% of patients in the carbazochrome sodium sulfonate group, respectively, and in 2%, 14%, 28%, and 14% of patients in the placebo group, respectively (110).
• A case report describes a patient with severe thrombocytopenia due to dengue hemorrhagic fever who was successfully treated with high-dose immunoglobulin (111).
• Recombinant activated factor VII was given to two children with acute bleeding resulting from liver failure and disseminated intravascular coagulation secondary to dengue hemorrhagic fever and prolonged shock. A bolus of 40 to 180 µg/kg followed by a continuous infusion of 16.5 to 33 µg/kg·h was given, which controlled the bleeding, shortened the prothrombin time, and significantly increased factor VII clotting activity (112).
• A review found the evidence base for benefit or lack of benefit of corticosteroids in patients with dengue to be limited. Previous studies were small, with methodologic flaws, less stringent randomization, and unclear allocation concealment, and were conducted a long time ago. Studies so far have only been in patients with dengue shock syndrome, and the possible effects of corticosteroids on thrombocytopenia and bleeding, as well as other complications of dengue, are unknown. All previous studies have been conducted in children. The effect of corticosteroid treatment in adults with dengue virus infection has not been evaluated (113).

Comments:

• Carbazochrome sodium sulfonate has been shown to block capillary permeability in an animal model.