Determinants of progression to refractory status epilepticus in low- and middle-income countries: A retrospective single-center analysis of treatment timing

Background: Status epilepticus (SE) is a neurological emergency associated with high morbidity and mortality. Benzodiazepines (BZDs) are recommended as first-line treatment within minutes of seizure onset; however, treatment delays remain common, particularly in low- and middle-income countries, where data regarding determinants of refractory status epilepticus (RSE) are limited. Methods: We conducted a retrospective single-center cohort study including consecutive patients aged ≥ 16 years with SE. The primary objective was to identify factors associated with progression to RSE, with particular focus on latency to first BZD administration. Multivariable logistic regression analysis was performed. Results: A total of 109 SE episodes were analyzed, of which 62 (56.9 %) progressed to RSE. Early BZD administration (≤30 min) occurred in 34.9 % of cases, whereas latency was undocumented in 14.7 %. Early treatment was more frequent in non-RSE than RSE episodes (48.9 % vs 24.2 %), while unknown latency was more common in RSE cases than non-RSE (22.6 % vs 4.3 %; p < 0.01). Two multivariable models were built, differing in how time to BZD was coded. In Model 1 (three-level time-to-BZD variable), undocumented latency was associated with RSE (OR = 9.3, 95 %CI:1.77–49.0; p = 0.01); administration beyond 60 min (OR = 2.4, 95 % CI:0.91–6.63; p = 0.09) and acute symptomatic etiology (OR = 2.2, 95 %CI:0.96–5.0; p = 0.06) were not. In Model 2 (dichotomized time-to-BZD), acute symptomatic etiology was independently associated with RSE (OR = 2.3, 95 %CI:1.05–5.22; p = 0.04). Conclusions: Undocumented latency to BZD administration and acute symptomatic etiology were independently associated with RSE, highlighting challenges of timely SE recognition and supporting efforts to standardize treatment pathways in resource-limited settings.