Steroids in severe head injury

Abstract

This is a prospective randomized study of the efficacy of steroid therapy in patients with severe head injury. One hundred patients were randomized into two equal groups: the steroid group received 5 mg/kg/day of methylprednisolone, and the nonsteroid group received no drug. The groups were similar in their clinical features. All patients received a standardized therapeutic regimen. The patients were also classified as early responders or nonresponders to the overall treatment protocol without regard to steroid administration, on the basis of change in Glasgow Coma Scale score during the first 3 days of admission. There was no statistically significant difference in the outcome of the steroid and nonsteroid group at 6 months. Of the responders who were on steroids, 74% had good outcomes or were disabled, compared with 56% of the responders who did not receive steroids. In the nonresponder group, the patients on steroids were actually associated with a worse outcome than those who did not receive steroids: 75% of the nonresponders who received steroids were dead or vegetative, compared to 56% of those who were not receiving steroids. The data suggest that: 1) the effect of steroids may be different for different patient groups; 2) in order to identify these patients, a sensitive coma scale is needed; and 3) a rational approach to steroid therapy in head-injured patients may be to start all patients on steroids, but to discontinue their use in patients identified as not benefiting from steroid therapy.

The far-reaching scope of neuroinflammation after traumatic brain injury

“…Corticosteroids, surprisingly, have been the least successful anti-inflammatory class of drugs in TBI (Table 3). Despite the potent effects on suppressing inflammation, high dose methylprednisolone (5 mg/kg/day), 167 “megadose” dexamethasone (100 mg), 168 “ultrahigh dose” dexamethasone (2.3 g), 169 the aminosteroid tirilazad, 170 and a trial of hydrocortisone and fludrocortisone (primary outcome hospital acquired pneumonia) 171 all failed to demonstrate benefits on neurological outcome. Off-target effects with systemic administration of corticosteroids likely impact outcomes, and in the case of tirilazad, limited brain exposure may have been a confounder.…”

Glucocorticoids and endothelial cell barrier function

“…However, in some other cases of CNS disease, it tends to aggravate the condition rather than diminish the negative effects. For instance, when GC treatment is applied to acute ischemic stroke, it is ineffective or even harmful (Saul et al 1981; Norris and Hachinski 1986; De Reuck et al 1988; Kumar et al 1989; Norris 2004; Poungvarin 2004; Roberts et al 2004). This is attributed to GC insensitivity at the hypoxic BBB.…”

Safety and Efficacy of Corticosteroid Use in Neurologic Trauma

“…Early studies found no significant difference in functional independence or mortality between patients treated with various corticosteroids and those who received placebo. 34 –37 However, many of these studies were limited by small sample size, poor study design, and inadequate concealment. 38 In 1997, Alderson et al published a meta-analysis of 13 randomized controlled trials that included 2073 patients with TBI of any severity who received corticosteroids within 7 days of injury.…”