Abstracts

Rationale:
Anti-seizure medication (ASM) dosing in pediatric convulsive status epilepticus (SE) varies, and under-dosing of first-line benzodiazepines (BZDs) is common. The relationship between ASM dosing and refractoriness to non-benzodiazepine ASMs (non-BZD ASMs) is unclear. We analyzed the impact of under-dosing the first and second-line treatments on the progression to pediatric refractory SE (RSE).
Method:
Retrospective analysis of prospectively collected data from January 2014 to May 2020 of pediatric patients with SE who received at least 2 ASMs. One group of patients failed to respond to the first non-BZD ASM dose (RSE) and the other group responded to the first non-BZD ASM dose [non-refractory SE (non-RSE)]. A low total BZD dose was defined as the BZD combination of repeated doses within the first 10 minutes of treatment onset that was lower than 100% of the minimum recommended dose. A low first non-BZD ASM dose was defined as a single dose lower than 100% of the minimum recommended dose. A logistic regression model was used, with low BZD dose and low non-BZD ASM dose as the main explanatory variables and RSE and non-RSE as the outcome variable, adjusting for confounders such as time to first BZD and time to first non-BZD ASM. We included an interaction term between BZD and non-BZD ASM low dose. A logistic regression model was also used to evaluate risk factors for low dosing of non-BZD ASM. In a subset of patients who received levetiracetam, an increasingly used second-line ASM with a wide recommended dose range, we evaluated the association of the levetiracetam dose range [lower dose range (20-40 mg/kg) and higher dose range (41-60 mg/kg)] in relation to progression to RSE (Fisher’s exact test).
Results:
Among 344 patients, 196 (57%) developed RSE, and 148 (43%) responded to the first non-BZD ASM dose (non-RSE) (Table 1). One hundred forty-eight (43%) patients received a low total BZD dose and 142 (41%) received a low first non-BZD ASM dose (Table 2). Sixty-nine (47%) patients with low BZD dose also received a low non-BZD ASM dose. Low first non-BZD ASM dose was not associated with age, sex, low BZD dose, intermittent SE, prior epilepsy, home ASM use, hospital SE onset, time to first BZD or time to first non-BZD ASM. The odds of developing RSE were not higher after a low total BZD dose (OR 0.77, 95%CI 0.48-1.24, p= 0.27) or a low first non-BZD ASM dose (OR 0.87, 95%CI 0.55-1.37, p= 0.54), with no significant interaction between low BZD dose and low non-BZD ASM dose. Levetiracetam was used in 40.1% of patients, and when comparing the dosing in the lower vs. the higher range to the proportion of RSE vs. non-RSE, we found no differences (p= 0.49).
Conclusion:
In this series, and unlike prior work showing that the time to first-line BZD treatment and low BZD dosing is related to longer seizure duration, under-dosing both BZDs and first non-BZD ASM was not associated with the progression to RSE, adjusting for time to treatment. Refractoriness of SE may be related to a variety of different factors, and some may be independent of the therapeutic approach.
Funding:
:ERF, PERF. CBA is funded by FAME.