Effect of Epilepsy and Antiepileptic Drug Therapy on Gastric Motility and Emptying by Comparing Gastric Volume With Point-Of-Care Gastric Ultrasound in Epileptic Patients After Standard CAS/ASA Fasting Guidelines

Epilepsy is a neurological disorder characterized by abnormal synchronous activity producing recurrent and unpredictable interruption of brain function and is diagnosed after two unprovoked seizures occurring at least 24 h apart. The prevalence of epilepsy is estimated to be between 0.5-2.2% with an annual incidence of 0.06%. As a result, anesthesiologists are almost certain to encounter these epileptic patients for both neurosurgical and non-neurosurgical procedures.

Currently, perioperative fasting guidelines advocated for epileptics are the same as those for the general population with fasting of 6-8 hours for solid food and 1 hour for clear liquids with the assumption of normal gastric emptying to minimize aspiration risk to zero. However, increasing evidence is emerging that assumptions of normal gastric emptying in epileptics patients might not be totally accurate and these patients might have high residual gastric volume and increased risk of aspiration and regurgitation during anesthesia induction.

The bidirectional impact of epilepsy on the gastrointestinal system is increasingly being recognized as functional gut-brain axis is disrupted through neural (vagal and sympathetic nerves), endocrine (e.g., gut hormones like ghrelin and cholecystokinin), and immune (e.g., cytokine-mediated inflammation) pathways by abnormal central nervous system hyperexcitability, chronic stress, and medication effects. Moreover, inflammatory factor stimulation by seizures, releases catecholamines and acetylcholine, which affect cholinergic transmission of gut sympathetic postganglionic nerves and thus, inhibit gut motility and increase gut transit time. In addition, seizures also impair GABAergic inhibitory control of hypothalamic paraventricular nucleus neurons and produce massive release of glucocorticoids, leading to increased cerebral excitability, triggering of a gut immune-inflammatory response and ultimately, increasing gut barrier permeability and reduced motility.

Furthermore, antiepileptic drugs (AEDs) have been associated with gastrointestinal side effects including gastric hypomotility and paresis. For instance, in a prospective study of 104 patients, two commonly used antiepileptics, carbamazepine and phenytoin, in overdosage, were associated with severe gastric hypomotility with gastric emptying half-times exceeding 120-300 minutes possibly due to anticholinergic properties, direct toxic effects on smooth muscle, or stress-induced autonomic dysregulation. Another antiepileptic drug, ethosuximide, is known to cause constipation and gastroparesis. Lamotrigine, an antiepileptic drug, has been shown in animal studies to cause gastroparesis by blocking L-type calcium channels, relaxing gastric smooth muscles and decreasing motility. Further, supporting evidence comes from a case report of severe gastroparesis involving a patient of refractory epilepsy on Lamotrigine and Vagal nerve stimulator, which required augmentation of VNS current settings for relief of gastroparesis.

Vagal nerve stimulation is an established therapeutic approach for managing drug-refractory epilepsy. Consequently, it can be inferred that some level of vagal nerve dysfunction may be present in individuals affected by drug-refractory epilepsy. As vagal parasympathetic efferents are key modulator of gastroduodenal motility by promoting peristalsis, any vagal nerve dysfunction is likely to disrupt normal gastrointestinal motility. In a study of healthy subjects, modulation of vagal tone via transcutaneous auricular VNS (taVNS) or deep slow breathing-enhanced antral contractions and increased the motility index, suggesting potential restorative effects on impaired motility. A similar effect of trans auricular vagal nerve stimulation on gastroduodenal motility was noted in healthy volunteers with increased gastric motility index and higher amplitude of peristaltic waves with high frequency stimulation, over low-frequency stimulation. Another factor influencing gastric motility in epileptics is the impact of ketogenic diets recommended for treatment of drug refractory epilepsy. Being high in fat and low in carbohydrates, ketogenic diets are likely to prolong gastric emptying and lowers the oesophageal sphincter tone and might be risk factor for aspiration during anesthesia induction despite adequate fasting time.