Lack of association of first and second-line medication dosing and progression to refractory status epilepticus in children.

作者信息

Barcia Aguilar Cristina, Amengual-Gual Marta, Brenton J Nicholas, Chapman Kevin E, Clark Justice, Gaillard William D, Goldstein Joshua L, Goodkin Howard P, Kahoud Robert, Lai Yi-Chen, Mikati Mohamad A, Morgan Lindsey A, Payne Eric T, Press Craig A, Reece Latania, Sands Tristan T, Sannagowdara Kumar, Sheehan Theodore, Shellhaas Renée A, Tasker Robert C, Wainwright Mark S, Zhang Bo, Loddenkemper Tobias

机构信息

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Pediatric Neurology Unit, Department of Pediatrics, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain.

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Pediatric Neurology Unit, Department of Pediatrics, Hospital Universitari Son Espases, Universitat de les Illes Balears, Palma, Spain.

出版信息

Seizure. 2024 Dec;123:133-141. doi: 10.1016/j.seizure.2024.10.017. Epub 2024 Oct 28.

PURPOSE

Evaluate the relationship between first and second-line medication dosing and progression to refractory status epilepticus (RSE) in children.

METHODS

This is a retrospective analysis of prospectively collected data from September 2014 to February 2020 of children with status epilepticus (SE) who received at least two antiseizure medications (ASMs). We evaluated the risk of developing RSE after receiving a low total benzodiazepine dose (lower than 100 % of the minimum recommended dose for each benzodiazepine dose administered within 10 min) and a low first non-benzodiazepine ASM dose (lower than 100 % of the minimum recommended dose of non-benzodiazepine ASM given as the first single-dose) using a logistic regression model, adjusting for confounders such as time to ASMs. The proportion of patients receiving low first non-benzodiazepine ASM doses was calculated and a logistic regression model was used to evaluate risk factors for low dosing of the first non-benzodiazepine ASM.

RESULTS

Among 320 children, 170 (53.1 %) developed RSE, and 150 (46.9 %) responded to the first non-benzodiazepine ASM dose (non-RSE). One hundred thirty-seven (42.8 %) received a low total benzodiazepine dose, and 128 (40 %) received a low first non-benzodiazepine ASM dose. The odds of developing RSE were not higher after a low total benzodiazepine dose (OR=0.76, 95 %CI 0.47-1.23, p = 0.27) or low first non-benzodiazepine ASM dose (OR=0.85, 95 %CI 0.42-1.71, p = 0.65). Receiving a low first non-benzodiazepine ASM dose was independently associated with having received a low total benzodiazepine dose (OR=1.65, 95 %CI 1.01-2.70, p = 0.04).

CONCLUSION

For most patients, dosing variability in first and second-line medications for SE was not the sole clinical feature predicting progression to RSE in this cohort of benzodiazepine-resistant patients. Identification of additional modifiable clinical biomarkers that predict progression to RSE is needed. Though lower ASM doses did not predict RSE in this model, the administration of ASMs at doses likely to prevent RSE remains crucial in SE treatment.