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Highly Refractory Status Epilepticus Associated with Increased Hospitalization Costs and Mortality

Highly refractory status epilepticus (SE) was linked with increased hospitalization costs and worse outcomes, according to a cross-sectional study published online on April 5 in JAMA Neurology.

SE hospitalizations were associated with  substantial mortality, morbidity, and costs, and were increasingly so with higher levels of refractoriness, reported Elan L. Guterman, MD, of the University of California, San Francisco and colleagues.

“More effective delivery of existing SE treatments and the development of new therapies may have the potential to prevent SE from progressing to a more refractory state, which could substantially decrease the need for ICU care, lower length of stay, and reduce the high clinical and economic burden of SE for patients and our health system," they wrote.

Using data from the Premier Healthcare Database, the researchers evaluated 43,988 hospitalizations for SE and collected information on patients with a primary or secondary diagnosis of SE; 51.9 percent of the cohort were men and the mean age was 49.9 years.

The study authors categorized patients based on the administration of antiseizure medications during hospitalizations. A high refractory state indicated an intensive care unit admission, therapy with more than one intravenous anesthetic, and one or more intravenous antiseizure drugs. Moderate refractoriness was defined for those whose treatment involved more than one intravenous antiseizure drug. And a low refractory state was defined as one in which patients took none or one intravenous antiseizure drug.

The researchers reported that 43.5 percent of the hospitalizations were for highly refractory SE, 23.1 percent for moderate refractory SE, and 33.4 percent for low refractory SE.

Across all levels of refractoriness, the median hospital length of stay was five days. Patients who were considered to be in a low and moderate SE refractory state were hospitalized three and four days, respectively, compared to an eight-day hospitalization for those who had highly refractory SE  (p<0.001 for all comparisons).

In-hospital mortality was 11.2 percent overall. Patients who were highly refractory had the greatest rate of mortality (18.9 percent), while those with low and moderate refractory SE had lower rates of mortality—4.6 percent and 6.3 percent, respectively (p<0.001 for all comparisons).

The median costs were $6,812 in the low, $10,592 in the moderate, and $25,105 in the high refractory cohorts (p<0.001 for all comparisons).

Limitations of the study include that the researchers excluded patients who were seen in the emergency department and whose hospitalization included transfer from or to an acute care facility and the potential for misclassification.​

Another limitation of the study was that the authors did not have information about long-term outcomes, like quality of life, cognitive change, functional dependence, and recurrent SE, outpatient health care use, long-term mortality, and outpatient costs, they added.

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Guterman EL, Betjemann JP, Aimetti A, et al. Association between treatment progression, disease refractoriness, and burden of illness among hospitalized patients with status epilepticus. JAMA Neurol 2021; Epub 2021 Apr 4.