Additional phenytoin is frequently needed in patients undergoing craniotomy for supratentorial tumour.

EDITOR: Phenytoin is generally prescribed to patients with supratentorial tumours to decrease the risk of seizures. Earlier studies showed that plasma phenytoin concentration may not be in the therapeutic range despite continued therapy [1]. During craniotomy for a supratentorial tumour, an intraoperative loading dose of phenytoin is generally used to prevent postoperative seizures [2,3]. In our institution, it has been common practice not to administer phenytoin intraoperatively. To understand the consequences of our practice of withholding intraoperative phenytoin, we measured perioperative serum phenytoin concentration in a group of patients undergoing supratentorial tumour surgery. We also tried to determine the factors influencing postoperative serum phenytoin concentrations. Twenty-five adult patients (ASA I or II) of either sex, receiving phenytoin for a period not less than 7 days before supratentorial surgery, were studied after institutional approval and informed consent. On the day of surgery, 300 mg of phenytoin was administered either orally or intravenously 4 h before surgery. The anaesthetic technique comprised of induction with thiopentone (5–6 mg kg), tracheal intubation facilitated by a muscle relaxant and maintenance with either isoflurane or propofol. Intraoperative analgesia was provided by fentanyl. Serum phenytoin concentration was measured before induction, immediately after surgery and 24 h after surgery. The assay, performed by a chemiluminescence technique using an Immulite Assay Kit (DPC; Los Angeles, CA, USA), permitted the measurement of total phenytoin concentration. The following parameters were recorded in all patients: duration of anaesthesia and surgery, volume of crystalloids, colloids and blood products administered, volume of urine output and blood loss, and occurrence of immediate postoperative seizures. A repeated-measures analysis of variance (ANOVA) with Bonferroni’s test was used to find out significant differences among the preinduction, immediate postoperative and delayed postoperative serum phenytoin concentrations. Study variables in patients with therapeutic and subtherapeutic concentrations of phenytoin were compared by one-way ANOVA for continuous data and a x-test for categorical variables. Pearson’s test was used to correlate preinduction phenytoin concentration and its decrease in the immediate postoperative period. Logistic regression analysis was used to determine the independent predictors of immediate postoperative subtherapeutic serum phenytoin concentration. A P value of ,0.05 was considered significant. There were 17 male and 8 female patients in the study. Their age was 386 12 yr and body weight was 56611 kg. Twelve patients had a preoperative history of seizures. The preinduction serum phenytoin concentration was highly variable among the patients (range 2.5–37.3mg mL (95% CI59.8– 17.8mg mL)). Despite continuous medication until the morning of surgery, 11 patients (44%) had a subtherapeutic concentration of serum phenytoin (normal range 10–20mg mL) in the preinduction sample. Serum phenytoin concentration was significantly lower in the immediate postoperative sample compared with the preinduction sample (9.567.0 vs. 13.869.4mg mL; P, 0.001). The concentration increased significantly in the delayed postoperative sample (11.86 8.0mg mL; P,0.001). The decrease in phenytoin concentration in the immediate postoperative sample correlated with its preinduction value (P,0.01; r50.8). Seizures within 24 h of surgery occurred in two patients. Only one of these patients had a preoperative history of seizures. Serum phenytoin concentration was within the therapeutic range (16.3 and 10.4mg mL) in both the patients. In the immediate postoperative period, serum phenytoin concentration was in a subtherapeutic range in 15 out of the 25 study patients. On univariate analysis, the variables that were significantly different between the therapeutic and subtherapeutic groups were the patient’s gender, preinduction phenytoin concentration, blood loss, blood transfusion, duration of surgery and duration of anaesthesia (Table 1). Of these, preoperative phenytoin level, intraoperative blood transfusion and the duration of surgery/anaesthesia were found to be the independent predictors of low serum phenytoin concentration in the immediate postoperative period (P,0.05). The value of prophylactic administration of antiepileptic drugs in patients with brain tumours remains controversial. Some authors claim a significant decrease in the incidence of seizures in the Correspondence to: G. S. Umamaheswara Rao, Department of Neuroanaesthesia, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India. E-mail: [email protected]; Tel: 191 8