Phenytoin plasma levels after intraoperative administration, for the prevention of post-craniotomy seizures

Since in a previous study (preliminary report) (18) the iv. administration of 15 mg X kg-1 of phenytoin (PNT) over 30 min in men produced toxic levels (25 micrograms/ml), a smaller iv. dose of 7 mg X kg-1 was given during anaesthesia to 80 patients under going craniotomy, for the prevention of post-operative seizures. Plasma PNT concentrations were studied in 22 patients before its iv. infusion 20 min, 40 min, and 1, 2, 3, 5, 8 and 12 hours later. Mean serum phenytoin levels were 9.3, 31.9, 27.8, 25.5, 19.4, 17.2, 15.4 and 19.2 micrograms/ml respectively. In this study it appeared that although the initial dose was 50% smaller than before, toxic levels were still encountered one hour after PNT administration (therapeutic range 10-25 micrograms/ml). Bearing in mind that in both our studies PNT appeared to have approximately the same efficacy in seizure prevention (from 95-97%), we suggest, that 7-10 mg X kg-1 would be adequate if administered as an intraoperative iv. infusion over an hour and that whenever possible serial serum levels should be monitored.