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. 2021 May 1;78(5):588-595.
doi: 10.1001/jamaneurol.2021.0520.

Association Between Treatment Progression, Disease Refractoriness, and Burden of Illness Among Hospitalized Patients With Status Epilepticus

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Association Between Treatment Progression, Disease Refractoriness, and Burden of Illness Among Hospitalized Patients With Status Epilepticus

Elan L Guterman et al. JAMA Neurol. .

Abstract

Importance: Status epilepticus (SE) is associated with poor clinical outcomes and high cost. Increased levels of refractory SE require treatment with additional medications and carry increased morbidity and mortality, but the associations between SE refractoriness, clinical outcomes, and cost remain poorly characterized.

Objective: To examine differences in clinical outcomes and costs associated with hospitalization for SE of varying refractoriness.

Design, setting, and participants: A cross-sectional study of 43 988 US hospitalizations from January 1, 2016 to December 31, 2018, was conducted, including patients with primary or secondary International Statistical Classification of Diseases, Tenth Revision, diagnosis specifying "with status epilepticus."

Exposure: Patients were categorized by administration of antiseizure drugs given during hospitalization. Low refractoriness denoted treatment with none or 1 intravenous antiseizure drug. Moderate refractoriness denoted treatment with more than 1 intravenous antiseizure drug. High refractoriness denoted treatment with 1 or more intravenous antiseizure drug, more than 1 intravenous anesthetic, and intensive care unit admission.

Main outcomes and measures: Outcomes included discharge disposition, hospital length of stay, intensive care unit length of stay, hospital-acquired conditions, and cost (total and per diem).

Results: Among 43 988 hospitalizations for SE, 22 851 patients (51.9%) were male; mean age was 49.9 years (95% CI, 49.7-50.1 years). There were 14 694 admissions (33.4%) for low refractory, 10 140 (23.1%) for moderate refractory, and 19 154 (43.5%) for highly refractory SE. In-hospital mortality was 11.2% overall, with the highest rates among patients with highly (18.9%) compared with moderate (6.3%) and low (4.6%) refractory SE (P < .001 for all comparisons). Median hospital length of stay was 5 days (interquartile range [IQR], 2-10 days) with greater length of stay in highly (8 days; IQR, 4-15 days) compared with moderate (4 days; IQR, 2-8 days) and low (3 days; IQR, 2-5 days) refractory SE (P < .001 for all comparisons). Patients with highly refractory SE also had greater hospital costs, with median costs of $25 105 (mean [SD], $41 858 [$59 063]) in the high, $10 592 (mean [SD], $18 328 [$30 776]) in the moderate, and $6812 (mean [SD], $11 532 [$17 228]) in the low refractory cohorts (P < .001 for all comparisons).

Conclusions and relevance: Status epilepticus apparently continues to be associated with a large burden on patients and the US health system, with high mortality and costs that increase with disease refractoriness. Interventions that prevent SE from progressing to a more refractory state may have the potential to improve outcomes and lower costs associated with this neurologic condition.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Guterman receives funding from the National Institute of Neurological Disorders and Stroke (1K23NS116128-01) and the National Institute on Aging (5R01AG056715), American Academy of Neurology as well as consulting fees from Marinus Pharmaceuticals Inc and personal compensation for serving in an editorial capacity for JAMA Neurology. Dr Betjemann has received personal compensation for serving in an editorial capacity for JAMA Neurology and as a consultant to the National Football League and Marinus Pharmaceuticals. Dr Strzelczyk reports personal fees and grants from Arvelle Therapeutics, Desitin Arzneimittel, Eisai, GW Pharmaceuticals, LivaNova, Marinus Pharmaceuticals, Medtronic, Sage Therapeutics, UCB Pharma, and Zogenix, outside the submitted work. Dr Aimetti, Joseph Hulihan, and Thomas Lyons are employees and shareholders of Marinus Pharmaceuticals Inc. Mr Li, Ms Wang, Mrs Yin, and Mr Miyasato are employees of Trinity Life Sciences, who were employed by Marinus Pharmaceuticals Inc, to conduct this research.

Figures

Figure.
Figure.. Patient Selection Flow Diagram
All patient encounters with a primary or secondary International Statistical Classification of Diseases, Tenth Revision diagnosis code specifying status epilepticus (SE) were identified. Outpatient encounters, emergency department encounters that did not lead to hospital admission, and hospitalizations that involved transfer to or from a different acute care hospital were excluded (eTable 4 in the Supplement).

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