Association Between Renin-Angiotensin System Inhibitors and Antiseizure Medication Burden in Critically Ill Patients With Status Epilepticus

Abstract

Background:

Status epilepticus (SE) often requires escalating antiseizure medication (ASM) therapy, increasing risks of hypotension, prolonged ventilation, and metabolic complications. The renin-angiotensin-aldosterone system (RAAS) has been implicated in neuronal excitability and neuroinflammation, yet its role in acute seizure management remains unclear.

Objective:

To evaluate the association between RAAS inhibitor exposure and ASM burden among critically ill adults with SE, and to assess treatment intensity based on total ASM administrations.

Methods:

We conducted a retrospective cohort study of adults with non-structural SE admitted to a tertiary neurocritical care unit between 2019 and 2024. Exposure was defined as administration of a RAAS inhibitor, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), during the intensive care unit (ICU) stay. The primary outcome was ASM burden, defined as the number of distinct ASMs administered during the ICU course. Continuous electroencephalogram reports were reviewed for electrographic seizure activity during the first 48 hours of monitoring. Negative binomial regression with log-transformed length of stay as an offset estimated incidence rate ratios (IRRs). Models were adjusted for age, hypertension, diabetes, and SE type, and validated using inverse probability of treatment weighting (IPTW).

Results:

Among 77 patients (17 RAAS inhibitor exposed, 60 non-RAAS inhibitor), RAAS inhibitor exposure was associated with a lower ASM burden (unadjusted IRR = 0.45; 95% confidence interval 0.24-0.83, P = 0.01). The association remained directionally consistent after covariate adjustment (IRR = 0.71 [0.38-1.34], P = 0.31) and after IPTW weighting (IRR = 0.63 [0.35-1.16], P = 0.14). Electrographic seizures were absent in the RAAS inhibitor group during the first 48 hours of EEG monitoring.

Conclusions and Relevance:

RAAS inhibitor exposure was associated with lower ASM utilization in critically ill patients with SE, with consistent direction across adjusted models. These findings support further investigation into RAAS modulation as a potential neuroprotective mechanism in acute epileptic states.