Dose- and time-dependent effects of dexamethasone on rat brain following cold-injury oedema.

Experiments were carried out with a rat model of brain-injury oedema to establish the most efficacious dose and administration schedule for dexamethasone treatment. The results indicate that there are statistically significant dose- and time-dependent effects for dexamethasone treatment of cold-injury oedema. The equivalent of a 500 mg dose of dexamethasone had the highest anti-oedematous effect. With higher doses no further improvement could be achieved and the potential of hazardous effects increased. As expected, pretraumatic drug treatment had the greatest therapeutic effect. Dexamethasone administration up to about 30 min after cold injury led to measurable beneficial results. Drug injection from 90 min or longer after injury only slightly reduced cerebral oedema. No therapeutic effects were found when dexamethasone was administered more than 21 hours after inducing cerebral oedema. If similar results are obtained in corresponding clinical studies, the recommended dexamethasone dose and schedule for treating traumatic cerebral oedema would be: 1) high doses of drug (e.g. 500 mg); 2) drug administration to begin as early as possible, preferably within the first 2-3 hours after head injury; and 3) treatment should be terminated within 2-3 days to avoid major side effects.