Effect of Epilepsy and Antiepileptic Drug Therapy on Gastric Motility and Emptying With Point-Of-Care Gastric Ultrasound

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.

Despite the obvious direct evidence and multiple extrapolatory insights from overdose studies, animal models, and healthy volunteer trials as explained above, there is a significant evidence gap. Prospective studies have not systematically evaluated preoperative gastric volumes in epilepsy patients, particularly in the perioperative settings. Gastric ultrasound remains an excellent noninvasive modality to determine the adequacy of fasting periods and to safely administer anesthesia while eliminating the risk of aspiration. Point-of-care ultrasound (POCUS) has emerged as a reliable, non-invasive bedside tool for assessing gastric content and volume qualitatively (e.g., empty, fluid, solid) and quantitatively (e.g., via antral cross-sectional area measurements), with validated formulas demonstrating high accuracy in predicting aspiration risk thresholds (>1.5 mL/kg).

This observational study aims to address this gap by measuring gastric volume and other surrogate markers of gastric emptying as described below in 30 consecutive epilepsy patients undergoing elective neurologic or non-neurologic surgery, aiming to determine if standard fasting protocols are adequate or if additional interventions (such as institution of liquid diet/prokinetics) are needed.

Informed, written consent will be obtained prior to the start of surgery.

Patients who provide consent to participate will have one gastric ultrasound performed in the preoperative preparation area. Each ultrasound will take approximately 5 minutes to perform and imaging will be done in both the supine position and right lateral decubitus (RLD) position. Ultrasound gel will be applied to the patient's abdomen and the ultrasound probe will be placed on the abdomen midline just below the sternum using a curvilinear probe (usually 2-5 MHz). The following imaging and assessment will be performed:

1. Gastric cross-sectional area: It will be assessed both in supine and Right Lateral Decubitus position as a full stomach (presence of solids or thick liquids) can be confirmed in the supine position but accuracy is significantly higher in RLD. Also, accuracy of gastric volume assessments is much higher in RLD position. To enhance consistency, surrounding structures will be identified and recorded in the following sequence: the stomach, left lobe of liver, pancreas, superior mesenteric artery, aorta, and inferior vena cava. Furthermore, if gastric POCUS reveals solids or thick liquids, patients will be labelled as full stomach and no further cross-sectional area (CSA) measurements will be attempted. However, if initial Gastric POCUS reveals clear fluids, CSA measurement will be done at the aortic level as measurements at the inferior vena cava (IVC) level yield false negatives and will include the full thickness of the gastric wall from serosa to serosa. The mean of three consecutive CSA measurements during the peristaltic contraction interval for the final analysis will be determined.
2. Peristalsis: Frequency of contractions will be noted over a full 3-minute period.

Patient demographics, age, biological sex, race, weight, height, BMI, comorbidities (e.g., Hypertension, Diabetes, Chronic Kidney Disease, etc.), and American Society of Anesthesiologists (ASA) status will be collected. Epilepsy characteristics as classified by the International League Against Epilepsy (ILAE) 2025 Guidelines, as well as record of anti-seizure medications (ASMs) (i.e., age at starting, duration of treatment, name, overdosage history, and history of drug refractory history) will be collected as well. Details regarding surgery (i.e., emergency/elective, type, fasting compliance), and pre-operative hemodynamics and investigations will also be collected. Finally, details regarding gastric ultrasound, including operator, time and date, probe, position, structures identified, gastric content, and cross-sectional area readings will be collected. A final gastric volume will be calculated from this data.