Seizure Disorder: Perioperative Considerations

Preoperative Considerations

• The incidence of perioperative seizures in patients with epilepsy is approximately 2–3%.¹
• Please see the OA summary on seizure disorder for more details. Link
• During the preoperative evaluation and interview, it is important to gain a complete understanding of the patient’s baseline disease status, manifestations, and current therapy.
• When discussing disease burden, key information to gather includes:
  • Frequency of seizures and date of the last seizure.
  • Physical manifestations of seizure, including laterality, motor involvement, and level of consciousness (both during the seizure and during the post-ictal period).
  • Typical duration of seizures and any history of status epilepticus.
  • Any history of hospitalizations or intubations for uncontrolled seizures.
• Outpatient medications should be reviewed, including:
  • Prescribed antiepileptic drugs (AEDs) and dosing frequency.
  • Any changes from the typical dosing schedule due to recent events, such as fasting in the perioperative period.
  • Any recent changes to therapy, including a change in dosage.
  • How breakthrough seizures are managed if they do occur, such as with benzodiazepines (which may include intranasal or rectal routes), and when the last time the breakthrough medication, if any, was used.
  • Other medications the patient is taking, with special attention to any drugs that affect hepatic cytochrome P450 (CYP) activity.
    • Common AEDs, including phenytoin, topiramate, and carbamazepine, are both metabolized by CYP isoforms and induce higher levels of hepatic CYP. Concomitant use or cessation of other CYP inducers or inhibitors can lead to unpredictable plasma levels of AEDs and alter the seizure threshold and/or contribute to sedation.
    • Notably, levetiracetam, a common first-line AED, does not meaningfully interact with the CYP system.
• AEDs should be continued throughout the perioperative period whenever possible.
• If a single dose of AED is missed, it should be taken as soon as possible after surgery. The decision to continue with surgery in the setting of a missed dose of AED depends on the type and urgency of surgery, frequency of breakthrough seizures, and a discussion with the patient regarding the risks of surgery and anesthesia.²
• If the patient has known seizure triggers, an approach to mitigate or avoid them should be discussed. Triggers can include the following, many of which may be experienced in the perioperative period:
  • Disruption in sleep schedule or changes in food/water intake.
  • Withdrawal from caffeine, drugs, or alcohol.
  • Bright or flashing lights.
  • Changes to or missed doses of AEDs.
• Assess if the patient has any stimulators in place, if they were recently reprogrammed or disabled, and if they have their own magnet or deactivation/control device available.

Intraoperative Management

Relevant Pharmacology

• Patients with seizure disorder who are taking AEDs often require higher dosing of anesthetic medications due to induction of CYP.
• Patients who are taking phenytoin or carbamazepine, which induce CYP 3A4, will more rapidly metabolize common anesthetic drugs, including midazolam, fentanyl, and rocuronium. More frequent redosing of these medications may be necessary.
• Sedatives:
  • Benzodiazepines and propofol act as CNS depressants, decreasing seizure activity and increasing the seizure threshold, making them preferred agents in patients with seizure disorder.²
  • Patients taking AEDs have been found to have a 10–15% lower dose requirement of propofol for induction of anesthesia.³
  • Ketamine has often been avoided as an induction agent as it is thought to lower the seizure threshold at lower doses. At moderate to high doses, however, it has some anticonvulsant properties, and recent studies have supported the safe use of ketamine in patients with seizure disorder.⁴
• Analgesics:
  • Most opioids are weak proconvulsants, but fentanyl and sufentanil are typically safe to use in patients with epilepsy.⁵
  • Remifentanil has gained favor in anesthesia for neurosurgical cases, including for epilepsy surgery; however, epileptiform activity in the setting of high remifentanil doses has been reported.⁶
• Inhalational agents:
  • There is some evidence linking high-dose sevoflurane, when combined with hypocapnia during pre-oxygenation and ventilation, to seizure-like activity in children.⁷ Additionally, sevoflurane has been found to induce more epileptiform activity than isoflurane.⁸
  • Isoflurane and desflurane have been successfully used in the treatment of refractory status epilepticus. For these reasons, isoflurane and desflurane are the preferred inhalational agents in patients with epilepsy.²
  • Some animal models have found nitrous oxide to precipitate seizure activity,² and seizures, while rare, have been reported in children following the use of nitrous oxide. It is thus recommended to avoid the use of nitrous oxide in patients with epilepsy.⁹
  • Enflurane, though now rarely used, can also precipitate epileptiform activity.

Intraoperative Monitoring

• Beyond the standard American Society of Anesthesiologists monitors, there are no specific guidelines for the intraoperative monitoring of a patient with a seizure disorder.
• EEG is the most accurate monitor for detecting seizure activity in an anesthetized patient, especially when paralyzed. However, the demands of EEG placement and training required for accurate interpretation often preclude their use in the intraoperative setting, unless a dedicated neuromonitoring team is used.
• BIS monitors can also detect seizure activity. While an increase in the BIS value is often seen during a seizure, with spike and sharp wave discharge, some studies have demonstrated no change10 or a paradoxical decrease in the BIS value. While BIS is not approved by the United States Food and Drug Administration for the detection of seizures, a change from the baseline waveform is likely the most effective method to detect seizure activity.

Management of Implanted Devices

• If a patient has an implanted vagus nerve stimulator (VNS), it should be reprogrammed to disable the vagal nerve stimulatory function before elective surgery.¹¹ Testing at the time of VNS implantation in some patients has precipitated bradycardia or asystole, and it is postulated that this could present in an unrelated surgery if the stimulator is left active.
• It is especially important to disable a VNS before spinal anesthesia, as increased vagal tone from the VNS can precipitate severe cardiac compromise when combined with spinal anesthetic-induced vasoplegia.¹¹
• Manufacturers generally recommend avoiding monopolar electrocautery anywhere in the body and bipolar electrocautery near the stimulator device. If electrocautery is to be used, the device should be turned off during the procedure and interrogated after the procedure is complete.
• In an emergency, most stimulators (responsive neurostimulation, VNS, and deep brain stimulation) may be disabled by placing a patient’s own magnet or a pacemaker magnet over it.

Management of Intraoperative Seizure

• While relatively infrequent, intraoperative seizures can be managed with propofol (10-20 mg, titrated to effect), midazolam, and/or levetiracetam (1000 mg).
• For patients on an AED, administration of an additional dose (if available intravenously) is recommended.
• Seizures that last for more than 5 to 10 minutes should be treated as status epilepticus (discussed separately).
• Please see the OA summary on intraoperative seizures. Link

Emergence

• As most general anesthetics increase the seizure threshold, emergence from and down-titration of these medications can precipitate seizure activity in patients who are at elevated risk for seizure.
• Some small-scale studies have found an association between seizure disorder and an increased risk of agitated or violent emergence from anesthesia.¹²
• Delayed emergence or persistently altered mental status after emergence should raise concern for status epilepticus or a postictal state.

Postoperative Care

• Epidemiological studies in patients with epilepsy have found that most perioperative seizures take place in the postoperative period, with children being more likely to experience a seizure. 1
• In the postoperative setting, management of acute, breakthrough seizures includes:
  • IV benzodiazepines such as midazolam (10 mg) or lorazepam (2–4 mg).
  • Careful monitoring for signs of airway compromise or respiratory depression, both during and after treatment of a seizure.
  • Administration of high-flow oxygen during the seizure.
  • Administration of supplemental oxygen for SpO₂ less than 94% in the post-ictal period.
  • A review of the home medication regimen for any missed doses.
  • The administration of a prophylactic, such as levetiracetam or phenytoin, should be considered.
• Patients with seizure disorder have also been identified as being at an elevated risk of post-operative stroke, though the reason for this is not fully understood.