Abstracts

Rationale: Intravenous third-line anesthetic agents (IV-TLA) are typically titrated in refractory status epilepticus (RSE) to achieve either seizure suppression or burst suppression on EEG. However, the optimum treatment paradigm is unknown, and little data exist to help guide clinicians in the weaning of IV-TLA in RSE. This study sought to evaluate several quantitative measures of EEG activity during IV-TLA weaning in RSE, employing a novel analytic technique to help predict which patients may successfully wean from IV-TLA. Methods: From a single-center database of continuous EEG data, we identified patients diagnosed with RSE who underwent at least one IV-TLA wean, excluding patients presenting with cardiac arrest. A successful IV-TLA wean was defined as the discontinuation of IV-TLA without recurrent seizure activity, whereas IV-TLA wean failure was defined as either recurrent seizures or an IV-TLA dose increase of at least 20% of the pre-wean dose (excluding the use of anesthetic specifically for comfort). EEG data were used to generate continuous maps of functional connectivity during each IV-TLA wean, and parameters characterizing the functional connectivity network were calculated and used to compare successful and unsuccessful weans. The signal power within defined EEG frequency bands was also calculated and compared between successful and unsuccessful weans.  Results: Twelve patients undergoing a total of 14 anesthetic weans (7 successes, 7 failures) were identified. Analysis of functional connectivity measures calculated from the EEG data revealed that successful IV-TLA weanings were characterized by the gradual emergence of larger, more highly-clustered networks of activity (Figure 1). To compare successful and unsuccessful IV-TLA weans, we averaged functional network parameters over a period of 30 minutes after the discontinuation of IV-TLA (but prior to the recurrence of seizures or resumption of IV-TLA in the case of unsuccessful weans). We found that functional networks from patients undergoing successful IV-TLA weans had a significantly higher mean density (0.076 vs. 0.044, p = 0.028), higher mean clustering coefficient (0.24 vs. 0.14, p = 0.027), fewer independent components (12.7 vs. 16.4, p = 0.006), and larger largest components (7.57 vs. 5.02, p = 0.015) than those from patients that failed anesthetic wean. Of note, there was no significant difference in the EEG power either within the alpha or delta spectral bands or in the alpha/delta ratio between successful and unsuccessful weans. Conclusions: We demonstrate that quantitative EEG measures in patients with RSE are modulated during IV-TLA weaning. We find that distinct patterns of changes in the networks of functional connectivity emerge during successful anesthetic weans that are absent in wean failures. Identifying EEG features that characteristically and dynamically emerge during successful versus unsuccessful IV-TLA weaning may help optimize anesthetic management for RSE by preventing an unnecessary excess of wean attempts or weaning duration. Funding: R25 NS065743