During the preoperative interview, the anesthesiologist determines and prescribes premedication for the patient. The choice of premedication can have major implications for the patient with epilepsy.

Administering antiepileptic drugs (AEDs)

Administering the patient's daily medications orally with a sip of water or via an alternate route (intravenously, intramuscularly, or rectally) can avoid decreasing serum levels into the subtherapeutic range. Not only AEDs but also antihypertensives and cardiac, diabetic, and asthma medications should be given in this way.

In non per os patients, AEDs may be given parenterally or rectally. If AEDs cannot be administered orally or parenterally (e.g., hyperemesis, gastrointestinal procedures, AEDs without parenteral forms), rectal administration is possible for some types see Table: Antiepileptic Drugs Available for Rectal Administration). (Although clonazepam has an intermediate absorption rate,10 the injectable forms of diazepam and lorazepam are rapidly absorbed rectally.11,12 A gel formulation of diazepam (Diastat) is rapidly absorbed rectally, with an absolute bioavailability of 90% relative to injectable diazepam. Diazepam rectal gel is an effective and safe treatment that is used to abort an episode of acute repetitive seizures in children.13 Carbamazepine can be given rectally with 80% absorption.14 When the liquid parenteral form of phenobarbital is administered rectally, 90% is absorbed in 4.4 hours.11 Phenytoin (liquid parenteral form) given rectally is slowly absorbed in dogs.15 Rectal absorption of oral forms of sodium valproate is complete, with peak concentrations occurring approximately 2 hours after administration.16

There is a need for close clinical monitoring during parenteral administration of AEDs in patients with renal, hepatic, or cardiac diseases. To minimize the incidence of adverse effects in this population, AEDs need to be administered at lower doses or infused more slowly. Monitoring therapeutic levels is essential to prevent postoperative seizures. Patients dying as a direct result of their epilepsy show a significantly greater incidence of subtherapeutic anticonvulsants than those dying of unrelated causes.17

Sedatives and analgesics

To calm the patient for transport to the operating room and to smooth induction, benzodiazepines (e.g., diazepam, midazolam, lorazepam), antihistamines (e.g., hydroxyzine), barbiturates, and opioids (e.g., meperidine, morphine) may be administered. The proconvulsant and anticonvulsant considerations of these medications are addressed on their individual pages.

Diminishing risks of complications

Careful choice of preoperative medications can diminish the risks of perioperative problems such as aspiration, hemorrhages, or postoperative nausea and vomiting.

Complications associated with aspiration are related to the volume (greater than 25–30 mL) and acidity (pH of less than 2.5) of the aspirated gastric fluid. Medications are administered based on their ability to increase gastric pH or decrease gastric volume. Histamine 2 antagonists (e.g., cimetidine, ranitidine, and nizatidine) increase gastric pH and are often administered to patients who are at high risk for aspiration (e.g., obesity, hiatal hernia). Although histamine 2 antagonists do not have proconvulsant activity, cimetidine can increase phenytoin plasma levels, and serum phenytoin blood levels should be monitored.

Metoclopramide is also prescribed for patients at risk for aspiration, because it increases low esophageal sphincter tone, facilitates gastric emptying, and has an antiemetic effect. This medication works both centrally and peripherally as a dopaminergic antagonist. Metoclopramide should be used cautiously in epilepsy patients because it may increase the frequency and severity of seizures.18

The role of valproate in inducing hemorrhage or exacerbating surgical blood loss is not clearly defined, but it has been suspected in the pathogenesis of hemorrhagic complications of surgery. Sodium valproate can cause thrombocytopenia and platelet dysfunction. The mechanism that underlies these effects is unknown. The presurgical evaluation of patients taking sodium valproate must include bleeding time and platelet count. Specific platelet function tests, such as platelet adhesiveness or aggregation, may also be helpful. There was a significant increase in the number of patients with abnormal bleeding times and a significant difference (p <.001) in blood loss during spine surgery in patients who took valproic acid as monotherapy.19 Other studies showed that valproic acid apparently did not increase complications of hemostasis during therapeutic surgical resections for epilepsy, and these studies did not recommend routinely discontinuing valproic acid before craniotomy.20 For major surgical procedures, another AED should be substituted, if possible. When valproate is used, dosages over 40 mg/kg per day should be avoided, because the hematologic effects of sodium valproate may be dose-related.21

Topiramate has several mechanisms of action, including inhibition of carbonic anhydrase, which may result in a normal anion-gap metabolic acidosis. This side effect can become clinically significant during surgery, especially with concomitant use of another carbonic inhibitor.22

Adapted from: Najjar S, Devinsky O, Rosenberg AD, et al. Procedures in epilepsy patients. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;499–513. With permission from Elsevier (www.elsevier.com).

Authored By: 
Orrin Devinsky MD
Souhel Najjar MD
Andrew D Rosenberg MD
Reviewed By: 
Steven C. Schachter MD
Wednesday, March 31, 2004