Perioperative implications of caring for patients with epilepsy

Published on 07/02/2015 by admin

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Perioperative implications of caring for patients with epilepsy

C. Thomas Wass, MD

Epilepsy is one of the most common neurologic disorders, with a prevalence approaching 1% of the population; nearly 3 million people in the United States have a seizure disorder. Seizures are characterized based primarily on the clinical manifestation and electroencephalographic (EEG) features (Box 138-1).

Box 138-1

Classification of Seizures *

Generalized seizures

Tonic-clonic (in any combination)

Absence with special features

Myoclonic absence

Eyelid myoclonia

Myoclonicationic

Epileptic spasms

*Seizure that cannot be clearly diagnosed into one of the preceding categories should be considered unclassified until further information allows their accurate diagnosis. This is not considered a classification category. however.

Bert AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010: 51(4): 676-685.

Anecdotal observations and case reports suggest that the process of anesthesia and surgery is associated with increased perioperative seizure activity (frequency and duration). Proposed etiologic factors include withholding antiepileptic drugs (AEDs) because of the patient’s NPO (nil per os) status prior to surgery, hypoglycemia, hyponatremia, hyperpyrexia, sleep deprivation, fatigue, stress, excessive alcohol consumption, and use of proconvulsant medications. Anesthetics (discussed in greater detail later) implicated in this response include inhalation anesthetic agents, local anesthetic agents (e.g., lidocaine, bupivacaine), opioids (e.g., fentanyl, alfentanil, sufentanil, meperidine), and some sedative-hypnotic medications (e.g., etomidate, ketamine, methohexital). Considering that these drugs are administered to most patients requiring general anesthesia, it is imperative to understand the effects of anesthetic agents on individuals with seizure disorders. Anesthesia providers must have an understanding of the implications of caring for patients with epilepsy who require anesthesia for non-neurosurgical operations, as well as the intricacies of providing anesthesia for patients with epilepsy undergoing resection of an epileptogenic focus.

Perioperative seizure frequency

The incidence of perioperative seizure activity in individuals without a history of epilepsy is unknown. In contrast, recent clinical investigations have provided information on the frequency of seizures in patients with a history of epilepsy undergoing either regional or general anesthesia. More specifically, in a study of 411 patients undergoing epidural, caudal, or peripheral nerve block, 24 (5.8%) experienced postoperative seizures. However, based on the temporal relationship (i.e., extended time interval) between local anesthetic administration and the seizure, it was unlikely that the regional anesthetic was the primary cause or a contributing factor. Similarly, Benish and colleagues observed that 6 of 297 (2%) patients with epilepsy undergoing general anesthesia experienced seizures. Of these 6 patients, only 1 (0.003%) required intravenous therapy to terminate the seizure. These studies show that, although many anesthetic medications (both regional and general) have proconvulsant properties, clinically relevant dosing was not temporally related to an escalation of perioperative seizure frequency. Rather, these authors concluded that perioperative seizure activity correlated more strongly with the patient’s underlying seizure history (i.e., baseline frequency) and number of AEDs than it did with the type of anesthesia to which the patients were exposed. Further, patients with a preoperative diagnosis of epilepsy did not appear to be at increased risk of experiencing anesthesia-related perioperative morbidity or of dying.

Effect of anesthetics on epilepsy

Inhalation anesthetic agents

Inhalation anesthetic agents (e.g., enflurane > sevoflurane) have both proconvulsant and anticonvulsant properties. At low doses, these inhalation anesthetic agents have the potential to induce EEG-identified epileptiform activity in individuals with or without a history of seizures. Although the mechanism of action has yet to be fully elucidated, these changes likely result from preferential inhibition of inhibitory central nervous system neurotransmission. As a result, excitatory neurotransmission is left unchecked in cortical and subcortical brain regions. In contrast, with escalating doses of the inhalation agents, the EEG progresses through a continuum of increased beta activity followed by burst suppression and, eventually, isoelectricity. Accordingly, inhalation anesthetic agents can be administered to facilitate cortical mapping during epilepsy surgery or (at higher doses) to terminate status epilepticus in patients whose seizures are refractory to conventional therapy.

Opioids

It is well established that opioids have the potential to induce epileptiform activity in both laboratory animals and humans. Opioid-induced epileptiform activity may be used to localize the epileptogenic zone activity in patients undergoing epilepsy surgery. Alfentanil, sufentanil, and remifentanil (i.e., short-acting opioids) may be used to “activate” epileptiform loci during intraoperative electrocorticography (ECoG) at the time of focal cortical resection. The cause of opioid-induced limbic system seizures has not been fully determined. Proposed mechanisms include selective activation of limbic opioid receptors, augmented release of excitatory amino acids (e.g., glutamate), and facilitation of coupling between excitatory postsynaptic potentials and somatic spike-generating sites or suppression of inhibitory interneurons (i.e., the disinhibition hypothesis). According to the disinhibition hypothesis, opioids indirectly excite limbic system structures by inhibiting neighboring γ-aminobutyric acid–secreting inhibitory interneurons.

Local anesthetic agents

Local anesthetic toxicity is a potential risk for all patients (both with and without epilepsy) undergoing regional anesthesia, particularly during procedures that require a large dose of local anesthetic agent, such as an epidural or caudal anesthetic or a peripheral nerve block. Systemic local anesthetic toxicity presents as a spectrum of neurologic symptoms and signs that worsen as plasma drug levels continue to rise. Symptoms of central nervous system toxicity generally follow a progression from lightheadedness, dizziness, and perioral numbness to visual or auditory disturbances (e.g., tinnitus). These symptoms are usually followed by peripheral muscle twitching and, ultimately, generalized tonic-clonic convulsions. As discussed earlier, a preoperative diagnosis of epilepsy does not appear to escalate the likelihood of local anesthetic-induced seizures in patients undergoing regional anesthesia.

Effect of antiepileptic drugs on perioperative patient care

The most relevant interaction between AEDs and anesthetic medications pertains to the use of nondepolarizing neuromuscular blocking agents (NMBAs) in patients chronically taking phenytoin, carbamazepine, phenobarbital. More specifically, this patient population may require a larger initial bolus dose of an NMBA to induce muscle paralysis, as well as more frequent dosing to maintain a steady-state plasma concentration. Although the cause has yet to be fully understood, the larger initial dose is —in part—related to increased plasma concentrations of α-acid glycoprotein (AAG), which is an inducible plasma protein responsible for binding basic drugs such as NMBAs. Thus, in the setting of chronic AED administration, AAG synthesis is increased, thereby decreasing the quantity of free (i.e., unbound, pharmacologically active) NMBA available to interact with nicotinic receptors at the neuromuscular junction. In regard to more frequent dosing, AEDs induce hepatic enzyme activity that, in turn, hastens metabolic inactivation of NMBAs.

Additionally, AEDs may cause hematologic perturbations (e.g., valproate can cause a dose-dependent thrombocytopenia), alter the results of liver function tests (γ-glutamyl transpeptidase, alkaline phosphatase, and alanine aminotransferase), and cause hepatotoxicity. Often, these alterations are not symptomatic and not thought to be clinically significant.

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