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Perioperative Seizures in Patients with a History of a Seizure Disorder

Niesen, Adam D., MD; Jacob, Adam K., MD; Aho, Lucyna E., RN; Botten, Emily J., RN; Nase, Karen E., RN; Nelson, Julia M., RN; Kopp, Sandra L., MD

doi: 10.1213/ANE.0b013e3181e534a4
Neuroscience in Anesthesiology and Perioperative Medicine: Research Reports

BACKGROUND: The occurrence of perioperative seizures in patients with a preexisting seizure disorder is unclear. There are several factors unique to the perioperative period that may increase a patient's risk of perioperative seizures, including medications administered, timing of medication administration, missed doses of antiepileptic medications, and sleep deprivation. We designed this retrospective chart review to evaluate the frequency of perioperative seizures in patients with a preexisting seizure disorder.

METHODS: We retrospectively reviewed the medical records of all patients with a documented history of a seizure disorder who received an anesthetic between January 1, 2002 and December 31, 2007. Patients excluded from this study include those who had an outpatient procedure or intracranial procedure, ASA classification of V, pregnant women, and patients younger than 2 years of age. The first hospital admission of at least 24 hours during which an anesthetic was provided was identified for each patient. Patient demographics, character of the seizure disorder, details of the surgical procedure, and clinically apparent seizure activity in the perioperative period (within 3 days after the anesthetic) were recorded.

RESULTS: During the 6-year study period, 641 patients with a documented seizure disorder were admitted for at least 24 hours after an anesthetic. Twenty-two patients experienced perioperative seizure activity for an overall frequency of 3.4%(95% confidence interval, 2.2%–5.2%). The frequency of preoperative seizures (P < 0.001) and the timing of the most recent seizure (P < 0.001) were both found to be significantly related to the likelihood of experiencing a perioperative seizure. As the number of antiepileptic medications increased, so did the frequency of perioperative seizures (P < 0.001). Neither the type of surgery nor the type of anesthetic (general anesthesia, regional anesthesia, or monitored anesthesia care) affected the frequency of perioperative seizures in this patient population.

CONCLUSIONS: We conclude that the majority of perioperative seizures in patients with a preexisting seizure disorder are likely related to the patient's underlying condition. The frequency of seizures is not influenced by the type of anesthesia or procedure. Because patients with frequent seizures at baseline are likely to experience a seizure in the perioperative period, it is essential to be prepared to treat seizure activity regardless of the surgical procedure or anesthetic technique.

Published ahead of print June 14, 2010

From the Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota.

Supported by the Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN.

ADN is currently at Austin Medical Center, Mayo Health System, Austin, MN.

Disclosure: The authors report no conflicts of interest.

Address correspondence and reprint requests to Sandra L. Kopp, MD, Department of Anesthesiology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905. Address e-mail to

Accepted March 29, 2010

Published ahead of print June 14, 2010

Seizures are a common occurrence in the general population, with an 8% to 10% lifetime risk of a single seizure and a 3% chance of a persistent seizure disorder.1,2 Therefore, patients with a seizure disorder make up a significant portion of individuals presenting for anesthesia and surgery. Despite this, no studies have reported the frequency of seizure activity during the perioperative period in patients with a seizure disorder. This information could be used to better counsel these patients regarding the likelihood of experiencing a seizure in the perioperative period, including possible factors that could affect this risk.

There are several factors that alter the risk of having a seizure, including but not limited to antiepileptic medication noncompliance, timing of antiepileptic medication administration, altered gastrointestinal absorption of antiseizure medications, electrolyte disturbances, and sleep deprivation.36 These are common conditions during the perioperative period. In addition, a number of medications routinely used in the perioperative period can affect the seizure threshold or have significant interactions with antiepileptic drugs.7

A recent review of patients with a seizure disorder who underwent a regional anesthetic technique estimated the frequency of perioperative seizures at 5.8% and concluded that the majority of postoperative seizures were related to the patient's underlying condition and that local anesthetic administration in this population is not contraindicated.8 However, there are no data estimating the overall perioperative seizure risk in patients with a known seizure disorder undergoing all types of anesthesia. This retrospective chart review was designed to evaluate the incidence of perioperative seizures in patients undergoing any type of anesthesia for nonneurologic procedures. The results of this chart review will allow a more accurate estimate of the risk for perioperative seizure in patients with a history of seizure disorder. Additionally, this study may identify factors that affect the likelihood of perioperative seizures in these patients.

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After IRB approval, we conducted a retrospective query of the Mayo Clinic Life Science System database from January 1, 2002 through December 31, 2007 to identify all patients who met the following inclusion criteria: age ≥2 years, hospital admission >24 hours' duration, received any anesthetic (general anesthesia, regional anesthesia, or monitored anesthesia care) during their hospital admission, and seizure disorder documented in the medical record before hospital admission. Patients with a seizure disorder were identified by searching for ICD-9 codes 345.0 to 345.91 and 780.3 to 780.39. From the 115,120 patients identified, the database was limited to those patients with one or more routine hospital admissions during the study period with a length of stay >2 days with an anesthetic administered during the hospitalization. A manual chart review was performed for these 1778 patients.

Patients were excluded if they had 1 of the following conditions: no confirmed seizure disorder (e.g., single febrile seizure in childhood, acute symptomatic seizure attributed to trauma, electrolyte disturbance, infection, or alcohol withdrawal), had anesthesia for an outpatient or intracranial procedure, were younger than 2 years of age, ASA V classification, or pregnant women who received a labor epidural as their sole anesthetic. For the 641 patients meeting inclusion criteria, the first hospital admission during which an anesthetic was provided for a nonneurolgic surgical procedure was manually reviewed for each patient. We defined the perioperative period as the time from the start of the surgical procedure until the third hospital day or hospital dismissal, whichever time period was shorter. Patient demographics including age, gender, ASA physical status, and urgency (elective or emergent) of the surgery were recorded. We recorded the characteristics and clinical course of the seizure disorder, including type of seizure disorder (simple partial, complex partial, generalized nonconvulsive, or generalized convulsive), seizure frequency, most recent seizure before surgery, previous surgical management for the seizure disorder, antiepileptic medications, other medications the patient was taking at the time of surgery, and blood levels of antiepileptic drugs within 2 weeks of the surgical procedure. If the patient had multiple seizure types at baseline, the most frequently occurring seizure type was recorded.

Details of the surgical procedure and the anesthetic were also documented, including type of surgical procedure, duration of inpatient stay (days), type of anesthetic (regional, general, monitored anesthesia care), primary induction drug, type of anesthetic maintenance, type of regional block, and use of any benzodiazepine during the anesthetic. For all patients identified as experiencing a clinically apparent seizure documented in the daily nursing and progress notes within 3 days after surgery, the circumstances surrounding the event were documented, including the time of seizure, type of seizure, recent local anesthetic administration, antiepileptic medications, medications administered at the time of the seizure, and recent antiepileptic drug blood levels. Information pertaining to the seizure activity was derived from anesthetic records, postanesthesia care unit notes, and daily progress notes of the primary service, medical consultation team(s), and the anesthesia pain service. The cause of the seizure was determined based on the frequency of preoperative seizures, antiepileptic drug levels, electroencephalographic results, radiographic imaging obtained, results from neurology consultation, and documentation detailing seizure activity.

Baseline patient and procedural characteristics were summarized using mean ± SD for continuous variables and frequency percentages for categorical variables. The frequency of postoperative seizures was summarized using a point estimate and exact 95% confidence interval. Baseline characteristics were compared between those who did and did not experience seizures using the rank sum test for continuous variables and the Fisher exact test for categorical variables. In all cases, a 2-tailed P value <0.05 was considered statistically significant.

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During the 6-year study period, 641 patients older than 2 years with a documented seizure disorder were admitted for at least 24 hours and had anesthesia for a nonneurologic surgical procedure. The mean age ± SD of patients was 52.8 ± 22.7 years. Other patient and procedural characteristics at the time of anesthesia and surgery are provided in Table 1. For these patients, the median (25th, 75th percentile) length of hospital stay was 4 (2, 7) days. There were 22 patients (3.4%; 95% confidence interval, 2.2%–5.2%) who experienced a seizure during the defined perioperative period. Using univariate analysis, patients with clinically apparent seizure activity postoperatively were found to be significantly younger than those who did not experience a seizure (40.3 ± 22.2 vs 53.3 ± 22.6 years; P = 0.011). Preoperative use of multiple antiepileptic medications (P < 0.001), shorter length of time between last seizure episode and hospital admission (P < 0.001), and more frequent seizures at baseline (P < 0.001) were all found to be associated with an increased risk for perioperative seizure (Table 2).

Table 1

Table 1

Table 2

Table 2

Of the 22 patients who experienced perioperative seizure activity, 19 patients had a seizure that was consistent with their usual seizure type. There was no association between anesthetic technique, induction drug, or type of maintenance and perioperative seizure occurrence. In addition, no relationship was found regarding surgical procedure type and perioperative seizure occurrence. Six patients had a documented subtherapeutic antiepileptic drug level. An additional 2 patients did not receive their antiepileptic medications per their usual schedule, 1 because of vomiting and 1 because of intestinal surgery. Antiepileptic drug levels were not assessed in these 2 patients (Table 3).

Table 3

Table 3

Two patients received regional anesthesia, but their seizures were not related to the regional block. One of these patients received a single-injection fascia iliaca block for postoperative pain control for a muscle biopsy. She experienced hundreds of complex partial seizures daily at baseline, and encountered these same seizures in the recovery room without any other signs or symptoms of local anesthetic toxicity. The second patient received a thoracic epidural catheter for postoperative pain control. The patient experienced complex partial seizures with secondary generalization at baseline, and had multiple generalized tonic-clonic seizures 24 to 48 hours postoperatively. The neurology service thought these seizures were his typical seizures and were likely triggered by hyponatremia (sodium level of 125 mmol/L). This patient also had subtherapeutic levels of phenytoin and phenobarbital at the time of the seizures.

Three patients had seizures that were different from their typical seizures. One patient had a complex partial seizure after antiepileptic medications were withdrawn because of Stevens-Johnson syndrome. This patient had a tracheostomy for prolonged airway management and was receiving a benzodiazepine infusion for sedation and seizure control at the time of this complex partial seizure, which was thought to be an isolated incident. The patient did have further seizures during hospitalization, but they were generalized convulsive seizures, which were typical for this patient. The other 2 patients who had seizures of a different type than their usual seizures had a history of seizures in the recovery room after previous anesthetics. Neither of these patients experienced frequent seizure activity at baseline, and a triggering cause could not be found during the previous episodes for either patient. Both of these patients also had clinically evident seizure activity in the recovery room during the current study period. The seizures were different than what was typical for each patient. Similar to the previous episodes, a triggering cause could not be identified.

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The definition of seizure is the clinical manifestation of abnormally hyperexcitable cortical neurons. Many people experience an isolated seizure during their lifetime (e.g., febrile seizure in children, acute symptomatic seizures caused by trauma, electrolyte disturbances, infection, and alcohol withdrawal) but are not regarded as having a seizure disorder. In Rochester, MN, the cumulative incidence of epilepsy through age 74 years is 3.0%, with an incidence of any seizure incident near 10%.9 Given this large segment of the population with a seizure disorder, it is not uncommon for these patients to present for surgery and anesthesia.

Recent data suggest that the occurrence of postoperative seizures in patients with a seizure disorder undergoing regional anesthesia is infrequent, and that regional anesthesia in such patients is not contraindicated.8 A multicenter prospective cohort study in Thailand reported an incidence of postoperative seizure of 3.1 per 10,000 for all patients undergoing all surgical (including neurosurgical procedures) and anesthesia types, but the incidence of postoperative seizure in patients with an underlying seizure disorder was not reported.10 Recently, a much smaller retrospective study examined the incidence of seizures in patients with epilepsy undergoing general anesthesia.11 Seizures were observed in 2% of patients and they reported no adverse effect after receiving general anesthesia.

There are many factors that can increase the likelihood of seizure activity in patients with a seizure disorder, including changes in antiepileptic drug levels, fatigue, stress, sleep deprivation, menstruation, electrolyte disturbances, and excessive alcohol intake.3,6,12 Many situations arise in the perioperative period that can affect antiepileptic drug levels, including preoperative medication noncompliance, changes in dosing schedule, perioperative medications, anesthetic exposure, and changes in gastrointestinal motility leading to delayed absorption and reduced bioavailability.3,5 In particular, when patients are advised to take nothing by mouth preoperatively, they may omit their scheduled doses of antiepileptic medications. This is exacerbated postoperatively in patients who are not allowed to take oral medications because of their surgical procedure or are unable to tolerate oral intake because of nausea and vomiting. Decreased antiepileptic drug serum levels may contribute to perioperative seizure activity.4

Nine patients in our study experienced perioperative seizure activity that was likely influenced by fluctuations in antiepileptic levels. Six of these patients had documented subtherapeutic antiepileptic levels, 2 had interruptions in their usual dosing schedule because of vomiting and nothing-by-mouth status, and 1 had antiepileptic medications intentionally withdrawn because of Stevens-Johnson syndrome. The therapeutic level for antiepileptic medications is a complex measurement that depends on the individual patient and the timing of the blood draw, and it frequently lies outside of the laboratory standard therapeutic range. However, the neurologists consulting on these cases thought that the levels obtained were below the therapeutic range for these particular patients, which contributed to their perioperative seizure activity. This underscores the importance of maintaining an inpatient dosing regimen as close as possible to what the patient is accustomed to as an outpatient. This can be challenging because a number of antiepileptics do not have a parenteral formulation and the interpretation of blood levels may be difficult for practitioners unfamiliar with these medications. Patients requiring multiple medications for seizure control present a particular challenge, because these patients are at a greater risk of seizure recurrence when medications are withdrawn or their dosage is reduced.13 Consultation with a neurologist may be necessary to formulate the most effective plan for these patients in the perioperative period.

The patients who experienced seizure activity perioperatively were significantly younger than patients who did not. In addition, the incidence of epilepsy is higher in the intellectually and developmentally disabled population, and there is increased morbidity and mortality in children with seizures and neurodeficits.14,15 This group of patients tends to have more frequent seizures and often requires anesthesia for routine procedures (e.g., radiologic examinations and dental examinations and treatment) or procedures related to trauma incurred during a seizure that a healthy patient otherwise would not require.16

In a recent study at our institution, 24 of 411 patients (5.8%) with a seizure disorder undergoing regional anesthesia experienced postoperative seizure activity, and none of these seizures were conclusively linked to the regional technique.8 The overall occurrence of postoperative seizures is slightly lower in our current investigation; however, it is unclear what factors may have contributed to this difference, because the anesthetic technique did not seem to significantly affect the rate of seizure activity. This study similarly found that patients whose last seizure occurred close to the time of admission were more likely to experience a seizure in the perioperative period. In addition, patients with more frequent seizure activity at baseline were more likely to have seizure activity during the perioperative period.

The retrospective nature of this study creates some limitations with regard to the recommendations that can be made based on the results. It is virtually impossible to retrospectively identify seizure activity in patients undergoing outpatient procedures, thus they were excluded from our study. However, the risk factors for perioperative seizures in outpatients are likely to be similar to those found for hospitalized patients in the perioperative period. Additionally, the retrospective nature of the study prevents us from making any specific recommendations regarding the perioperative management of patients with a seizure disorder. Both of these issues would require further prospective investigation. The lack of continuous electroencephalographic monitoring in our study may have caused an underestimation of the overall seizure frequency. In addition, there may have been patients with nonconvulsive seizures resulting in prolonged emergence or nocturnal nonconvulsive seizures that were not identified.

In summary, patients with an underlying seizure disorder infrequently experience a perioperative seizure. Patients with frequent seizures at baseline and with recent seizures before surgical admission are at increased risk for perioperative seizure activity. The anesthetic technique does not seem to have a role in the occurrence of perioperative seizures, and most patients who do have a seizure experience their typical seizure type. The patient's usual antiepileptic medication regimen should be followed as closely as possible the day of surgery and while hospitalized, with parenteral formulations of the patient's usual medications used if gastrointestinal access is contraindicated or if absorption could be affected. The anesthesiologist should also be prepared to treat seizure activity in the perioperative setting, particularly in those patients who have frequent seizures at baseline and those who have experienced seizure activity close to the time of admission.

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This research was conducted as part of the research requirement for the Masters of Nurse Anesthesia Program through the School of Health Related Sciences, Mayo Clinic (for LEA, EJB, KEN, and JMN).

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