Highly refractory status epilepticus associated with worse outcomes, high hospital costs
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Status epilepticus incurred “a large burden” on patients and the U.S. health care system over a 3-year study of more than 43,000 hospitalizations, with higher mortality risk and hospital costs as disease refractoriness increased.
Researchers published the results in JAMA Neurology.
“We have a theoretical understanding that patients who have more severe forms of status epilepticus have worse mortality, worse morbidity and carry a large financial burden on the health system, but we previously lacked data from large, nationally representative cohorts systematically quantifying this,” Elan L. Guterman, MD, assistant professor of neurology at the University of California, San Francisco, School of Medicine, told Healio Neurology. “This study was designed to fill that gap in the literature so we can better understand the clinical need and potential benefits to improving care for patients with more refractory forms of status epilepticus.”
Guterman and colleagues aimed to determine differences in clinical outcomes and costs for 43,988 hospitalizations (51.9% men; mean age, 49.9 years) in the United States between January 2016 and December 2018 for status epilepticus of varying refractoriness. They specifically assessed discharge disposition, hospital and ICU length of stay, hospital-acquired conditions and costs among the cohort.
The researchers categorized patients into one of three groups: Low refractoriness to treatment with none or one IV anti-seizure drug (n = 14,694), moderate refractoriness to treatment with more than one IV anti-seizure drug (n = 10,140) or high refractoriness to treatment with one or more IV anti-seizure drug, more than one IV anesthetic and ICU admission (n = 19,154).
Most patients (45.2%) had Medicare as their primary payer, followed by Medicaid (27.9%) and commercial plans (4.7%). Common etiologic factors among the 27.8% of patients who were classified as having a suspected source of status epilepticus included hyponatremia (10.4%), acute ischemic stroke (6%), central nervous system tumor (4.4%) and alcohol withdrawal (3.1%).
Results showed that overall in-hospital mortality was 11.2%, of which 18.9% occurred among patients with highly refractory disease, 6.3% among those with moderate refractoriness and 4.6% among those with low refractoriness (P < . 001 for all).
When the researchers combined data on in-hospital mortality and discharge to hospice, they observed increased in-hospital mortality rates of 25.3% among those with high refractoriness, 13.6% increase among patients with moderate refractory and 7.9% with low refractory (P < .001 for all).
In addition, decreases were observed in the proportion of patients who were discharged home from 60.7% among those with low refractoriness to 44.4% among those with moderate refractoriness and 34.4% among those with high refractoriness.
The researchers reported a median length of hospital stay for the overall cohort of 5 days (interquartile range [IQR], 2 days to 10 days) whereas median length of hospital stay among those with high refractoriness was 8 days (IQR, 4 days to 15 days), followed by 4 days (IQR, 2 days to 8 days) among those with moderate refractoriness and 3 days (IQR, 2 days to 5 days) among those with low refractoriness (P < .001 for all).
Hospital-acquired conditions occurred among 19.2% of all admissions. Of these, the researchers observed the highest proportion among those with high refractoriness and urinary tract infection was the most common (16%). Suspected causes of hospital-acquired infections included meningoencephalitis (31%), hyponatremia (29%), ischemic stroke (29%) and intracerebral hemorrhage (26%).
Guterman and colleagues additionally observed higher median hospital costs among patients with high refractoriness ($25,105) compared with those with moderate refractoriness ($10,592) and those with low refractoriness ($6,812; P < .001 for all).
Limitations of the study included the fact that the study results are likely to underestimate the cost of status epilepticus for patients and the health care system; there is the potential for misclassification of statis epilepticus; and patients whose hospitalization involved transfer to or from another acute care hospital and who were seen in the emergency department were excluded.
“Status epilepticus is dangerous and costly,” Guterman said. “Across all forms of status epilepticus, the mortality rate is 11% and, in the subgroup of patients who have very medically refractory seizures, it is even higher — nearing 20%. Although we have effective medications to stop seizures, patients are hospitalized an average of 5 days and hospital costs are on average $26,304.”
Results from the current study “provided an important comparison for how certain factors change as seizures become increasing refractory to medications,” Guterman added.
“If we can block the cascade of seizures and prevent status epilepticus from becoming so medically refractory, then hopefully we can improve outcomes for these patients,” she said. “Despite increasing the number of medications that we use to treat seizures and improving how we provide neurocritical care, we have consistently failed to improve mortality for patients who are hospitalized with status epilepticus. My goal is to continue doing research that will address the systems issues driving this stagnation and identify opportunities that we have to improve patient outcomes for those with status epilepticus.”