[Cerebral blood flow and indomethacin. The effect of different doses administered as continuous intravenous infusions or as suppositories in healthy adults].
Administration of indomethacin may aid treatment of intracranial hypertension, and the present study was conducted to determine the optimal dose. In healthy volunteers, cerebral blood flow (CBF) has been shown to decrease considerably after a bolus dose of indomethacin, 0.4 mg/kg, followed by continuous infusion, 0.4 mg/kg/h. This decrease was sustained for 6 h without any evidence of adaptation. In a randomized study in healthy volunteers, indomethacin, 0.1, 0.2 and 0.3 mg/kg, was given as bolus, followed by continuous infusion of 0.1, 0.2 and 0.3 mg/kg/h. CBF decreased from normal levels (52-74 ml/100 mg/min) to 38-51 ml/100 g/min. There were no differences among the three groups in CBF reduction, and the reduction was sustained during the 6-h infusion period. Rectal application of 100 mg indomethacin was found to reduce CBF from normal levels (54-74 ml/100 mg/min) to 33-48 ml/100 mg/min. These low levels were only sustained for 2 h, and values returned to normal over the next 6 h. We observed no rebound phenomenon 2 h after stopping the infusion and no rebound after 100 mg of rectally applied indomethacin. Since a dose as low as 0.1 mg/kg/h is effective, it is possible to treat most patient in a 24-h schedule without going over maximum recommended doses.