Indomethacin: A review of its cerebral blood flow effects and potential use for controlling intracranial pressure in traumatic brain injury patients

Traumatic brain injury (TBI) causes about 75,000 deaths and leaves approxim ately 200,000 people disabled in USA each year. Brain swelling and increase d intracranial pressure (ICP) contribute to this morbidity and mortality. A ggressive management protocols,including ICP control, have been shown to re duce the overall mortality from 50% to 36% following severe head injury. De spite these encouraging results, new and improved pharmacologic strategies to control ICP are required. Indomethacin (IND) is a non-steroidal anti-inf lammatory agent with unique effects on cerebral blood flow physiology which may be of benefit in reducing elevated ICP in TBI patients. Data from anim al models and randomized, controlled studies with pre-term infants have sho wn that i.v. IND produces rapid, significant reductions in cerebral blood f low (CBF). Controlled studies of i.v. IND in normal volunteers show a reduc tion in CBF from 26%-40%. Case series involving severe TBI patients suggest that IND i.v. boluses of 30-50 mg reduce ICP by 37%-52%, reduce CBF by 22% -26%, with a modest 14% increase in cerebral perfusion pressure (CPP). Desp ite these encouraging results, i.v. IND should only be considered an experi mental treatment for control of refractory ICP in TBI patients. Larger, wel l-designed randomized trials in TBI patients will provide more efficacy and safety data and delineate the effects of IND alone or in combination with other proven, effective, or experimental therapies. Once these concerns hav e been addressed, larger outcome studies will ultimately be needed to deter mine the role of IND for ICP control in TBI patients.