Anesthesia-Related Perioperative Seizures:

Pathophysiology, Predisposing Factors and

Practical
Recommendations
AEDs and anesthetic drugs

• However many AEDs induce or inhibit the expression of cytochrome

P450 isoenzymes thus modifying the metabolism of many drugs used
in general anesthesia
• Phenytoin, carbamazepine, phenobarbital, and primidone stimulate
the metabolism of fentanyl, vecuronium and other non-depolarizing
neuromuscular agents, as well β-blockers, (propranolol, and
metoprolol), and calcium channel antagonists, (nifedipine, felodipine,
nimodipine, and verapamil).
Sleep deprivation

• Sleep deprivation (SD) predisposes to clinical seizures as well as

epilepticform discharges on the EEG [29] even in patients with no
prior seizure history.
• Transcranial magnetic stimulation studies suggest increased cortical
excitability in sleep-deprived patients.
• Selective rapid eye movement (REM) SD signi cantly reduces silent
period duration and intracortical inhibition
• These SD modi cations in cortical excitability may be mediated by
GABA ergic neurons
Fatigue and Stress

• Patients report stress and tiredness as factors that precipitate seizures

and increase their frequency.
• In their series, emotional stress and tiredness were among the three
most commonly reported factors (20.9% and 9.5% respectively) with
equal distributions between generalized and partial seizures
• Mechanisms on how the stress can predispose to seizures are not
fully understood.
Hyperventilation

• Hyperventilation is associated with a decline in PCO2 and subsequent

decrease in cerebral blood flow. These changes tend to decrease the
normal alpha and beta activity on the EEG and induce a synchronous
delta activity (<4 Hz). The epileptogenic effects of hypocapnia have
been used as a diagnostic tool during electrophysiological diagnosis of
epilepsy
• According to Holmes, only 0.52% of patients with localized epilepsy
and no patient with generalized seizures developed clinical seizures in
response to hyperventilation.
Local anesthetics
• CNS compromise resulting from the local anesthetic-induced systemic
toxicity (LAST) is well recognized. e overall estimated incidence of
perioperative seizures related to local anesthetic toxicity is 120 per
10,000
• In lower doses, local anesthetics produce an antiepileptic action,
while proepileptic e ects become more pronounced a er increasing
the dose and plasma concentration.
• One of the explanations of the neurotoxic e ects of local anaesthetics
is their ability to rapidly cross the blood–brain barrier and decrease
seizure threshold in the hippocampus, cerebral cortex and amygdala,
predisposing the patient to seizures.
Volatile agents

• The pro-convulsant potential of volatile agents is explained by their

ability to destabilize the cortex and delay inhibitory circuits
• desflurane produced less cortical spikes compared to other
inhalational anesthetics at a maintenance dose. The agents could be
ranked by their relative ability to cause spike activity: enflurane >>
sevoflurane > isoflurane = desflurane
Intravenous agents

• Propofol at low doses can induce both epilepticform activity on EEG

and overt seizures during anesthesia induction and emergence. is
may be explained by rapid changes of propofol concentration in the
brain at the beginning or end of anesthesia. Glycine antagonism and
speci c GABAA receptor agonism appear to mediate the epileptogenic
potential of propofol
• According to Hadipour- Jahromy and Daniels, propofol increases the
inhibition of GABA ergic thalamopetal inputs to the thalamus,
generates thalamo-cortical oscillations and promotes high-voltage
spike and wave spindles and clinical seizures in animal models.
Ketamine
• Ketamine acts on NMDA glutamate receptor as a noncompetitive
antagonist. Although some cases of ketamine induced seizures have
been published in animals
Opioids

• Neuro excitatory activity has been described for hydromorphone,

morphine, meperidine, remifentanil and fentanyl
• Experimental models suggest that neuronal excitation is mediated via
selective stimulation of κ and μ opioid receptors in a dose-dependent
manner, decreased GABA ergic interneuronal inhibition of pyramidal
neurons and inhibition of hyperpolarization-activated K+ currents