The Impact of Antiepileptic Therapy on Anesthetic Requirements and Postoperative Pain in Patients with Pharmacoresistant Focal Epilepsy: A Retrospective Study

ABSTRACT
Background: Patients with pharmacoresistant focal epilepsy (PRE) are exposed to long-term antiepileptic drug (AED) therapy, which may influence anesthetic pharmacology and postoperative pain. However, evidence regarding the perioperative effects of chronic AED treatment remains scarce. The study aims to investigate the association of AED regimen, epilepsy duration, anesthetic consumption, and surgery with postoperative pain in patients with pharmacoresistant focal epilepsy.
Methods: The retrospective cohort study included 92 participants with pharmacoresistant focal epilepsy who underwent neurosurgical intervention between 2019 and 2024. Patients were stratified according to AED regimen into carbamazepine monotherapy (n=27), carbamazepine plus levetiracetam (n=44), and other AED combinations (n=21). Intraoperative anesthetic consumption, postoperative visual analogue scale (VAS) pain scores, analgesic requirements, and perioperative outcomes were compared. Predictors of postoperative pain were evaluated using multivariable logistic regression analysis.  
Results: Patients receiving combination AED therapy had significantly longer epilepsy duration than those receiving carbamazepine monotherapy (median 16–18 vs. 8 years, p<0.01). Intraoperative consumption of fentanyl, propofol, sevoflurane, and neuromuscular blocking agents did not differ among treatment groups (all p>0.05). Postoperative pain occurred in 58.7% of patients, with similar VAS trajectories, analgesic requirements, and time to first analgesic request across groups. Surgery type was not associated with postoperative pain in either univariate or multivariable analyses. Multivariable logistic regression demonstrated no independent association between postoperative pain and AED regimen, intraoperative fentanyl dose, sex, or surgical procedure (all p>0.05). Sensitivity analysis limited to patients receiving carbamazepine or levetiracetam as the primary AED yielded consistent results, although levetiracetam showed a non-significant trend toward lower odds of postoperative pain compared with carbamazepine (adjusted OR 0.47, 95% CI 0.19–1.18).
Conclusions: Long-term AED regimen, epilepsy duration, and surgery type were not independently associated with anesthetic requirements or early postoperative pain in patients undergoing surgery for pharmacoresistant focal epilepsy. Standardized perioperative anesthesia and postoperative analgesia appear to provide effective pain control regardless of chronic AED therapy. Larger prospective multicenter studies are needed to confirm these findings and evaluate the perioperative effects of individual AEDs.
Keywords: pharmacoresistant focal epilepsy; antiepileptic drugs; carbamazepine; levetiracetam; postoperative pain; anesthesia; epilepsy surgery; neurosurgery.