ObjectiveTo investigate the benefit of the hyperosmolar agent, mannitol, and the xanthine oxidase inhibitor, allopurinol, in experimental pneumococcal meningitis in the rat.DesignA prospective, randomized, controlled experimental study.SettingExperimental animal laboratory in a university hospital.SubjectsSixty-five anesthetized and artificially ventilated adult male Wistar rats, weighing 250 to 300 g.InterventionsMeningitis was induced by intracisternal injection of live pneumococci. Infected rats were randomized to receive mannitol or allopurinol.Measurements and Main ResultsThere were marked increases in regional cerebral blood flow (measured by laser-Doppler flowmetry), intracranial pressure, brain water content, and cerebrospinal fluid white blood cell count in infected rats within 6 hrs after infection (p < .05, compared with uninfected controls). Continuous infusion of mannitol (0.6 g/kg/hr iv), started just before infection, attenuated the increases of regional cerebral blood flow, intracranial pressure, and brain water content (p < .05, compared with untreated infected rats 6 hrs after infection). When continuous mannitol treatment was started 4 hrs after infection, intracranial pressure at 6 hrs was significantly lower than in untreated infected rats. When mannitol was given by a bolus injection (1.5 g/kg iv) at 4 hrs after infection, intracranial pressure measured 0.5 hr thereafter was consistently reduced in all animals (intracranial pressure reduction by 21.3 +/- 5.1 [SEM] %). Pretreatment with allopurinol (150 mg/kg iv) did not significantly influence regional cerebral blood flow, intracranial pressure, and brain water content in pneumococci-injected rats. Both agents, mannitol and allopurinol, did not inhibit cerebrospinal fluid pleocytosis in infected rats. In uninfected rats, mannitol significantly increased regional cerebral blood flow by a nitric oxide-independent mechanism, whereas allopurinol slightly decreased blood flow.ConclusionsMannitol attenuated pathophysiologic changes in experimental pneumococcal meningitis. One possible mechanism of the mannitol effect might be scavenging of hydroxyl radicals which have been shown to be involved in the pathophysiology of pneumococcal meningitis. The failure of allopurinol to modulate pathophysiologic parameters may suggest that during early experimental pneumococcal meningitis in the rat, the xanthine oxidase pathway seems not to be a major source of reactive oxygen species.(Crit Care Med 1996; 24:1874-1880)