Dexamethasone effect on the inflammatory response of the central nervous system in bacterial meningitis

Abstract

In northern Europe, Canada, and the United States, the incidence of invasive infection by Haemophilus influenzae type b (HIB) in the pediatric population has been reported to be 40 to 70 per 100,000 children. In Costa Rica, the incidence of meningitis caused by HIB has been estimated to be 40 to 60 per 100,000 in children younger than age 5 years, and the incidence of other invasive infection such as epiglottitis, septicemia, pneumonia, arthritis, and pericarditis has been estimated to be 20 per 100,000 in children under 5 years of age. In bacterial meningitis, the bacteria that have invaded the cerebrospinal fluid (CSF) proliferate, undergo degradation, and release toxins, or teichoic acid. The inflammatory response of the central nervous system is activated and the principal mediators have been shown to be interleukin-1β (IL-1β), tumor necrosis factor (TNF), platelet aggregation factor (PAF), polymorphonuclear cells, and macrophages. After encouraging results in animal models, dexamethasone was used in infants and children with purulent meningitis, to modulate the inflammatory response. When dexamethasone was administered 15 to 20 minutes before the first dose of cefotaxime, the mean CSF pressure, and the estimated cerebral perfusion pressure 12 hours after initiating therapy improved significantly in the patients who received dexamethasone. Twelve hours after dexamethasone the signs of meningeal inflammation and the concentrations of 1L-1β, TNF-α, and PAF had significantly decreased compared with the control patients. At the 15-month follow-up visit, 7 (14%) of the 51 survivors who received dexamethasone and 43 (90%) of the 48 controls who survived had one or more audiologic or neurologic sequelae ( P = 0.007). To achieve beneficial effects in the treatment of purulent meningitis, dexamethasone should be administered at a dosage of 0.15 mg/kg, 15 to 20 minutes before the first dose of parenteral antibiotics, and every 6 to 8 hours thereafter, for a total of 2 to 4 days. Dexamethasone should not be administered to patients with suspected or documented viral meningitis. The accumulated data in the literature regarding the benefits of dexamethasone pertain mainly to meningitis caused by HIB; however, there are experimental reports, as well as studies in infants and children, that show its effectiveness in the treatment of bacterial meningitis caused by Streptococcus pneumoniae. Further studies, as well as a meta-analysis of past and more recent studies, are needed.