BOSTON – Survivors of sepsis face a significantly increased risk of seizures following an index hospitalization, regardless of any previous history of seizures or seizures occurring during hospitalization, according to findings from a retrospective, population-based cohort study.
The risk for having subsequent seizures was highest for patients younger than 65 years but was still elevated above the general population for those aged 65 years or older, Michael Reznik, MD, reported at the annual meeting of the American Academy of Neurology.
Seizures are already a well-known complication of sepsis, and they also can occur alongside sepsis-associated encephalopathy, stroke, and neuromuscular disease. The frequency of sepsis-associated encephalopathy also has led to the recognition of postsepsis cognitive dysfunction, said Dr. Reznik, a neurocritical care fellow in the department of neurology at Weill Cornell Medicine and Columbia University Medical Center in New York.
It is unclear, however, how much of the risk for cognitive impairment after sepsis is due to pre-existing cognitive impairment, frailty, or lingering sedation effects, he said.
It’s possible, he noted, that “seizures may be more specific for structural brain injury, and I think our findings may support the hypothesis that sepsis could be associated with pathways leading to long-lasting brain injury that’s independent of other primary injuries that we have controlled for.”
Dr. Reznik and his coinvestigators used administrative claims data from all discharges from nonfederal emergency departments and acute care hospitals in California, New York, and Florida during 2005-2013 that had been collected as part of the federal Healthcare Cost and Utilization Project (HCUP). The HCUP assigns each patient a unique number that can be used to follow them anonymously through all subsequent hospitalizations. At each encounter, HCUP also tracks up to 25 discharge diagnoses that were present before hospital admission or developed during hospitalization, based on ICD-9-CM codes.
The investigators excluded patients with an ICD-9-CM diagnosis of seizures either before or during the index hospitalization for sepsis.
Overall, the 842,735 adult sepsis survivors in the study had a 6.67% cumulative rate of seizures over the 8-year period, compared with 1.27% in the general population. This translated to an incidence of about 1,288 per 100,000 patient-years in sepsis survivors, compared with 159 per 100,000 patient-years in the general population. The overall incidence rate ratio (IRR) for seizures among sepsis survivors was about 5, but was higher for those who also had neurologic dysfunction (such as encephalopathy, delirium, coma, or stupor) during their index hospitalization than in those without it (7.52 vs. 4.53). Sepsis survivors also had an elevated IRR of 5.42 for status epilepticus.
Sepsis survivors also had an elevated IRR of 4.35 for seizures when compared against control patients who were hospitalized for diagnoses other than sepsis and matched for age, sex, race, insurance, length of stay, discharge location, year of hospitalization, state, and the presence of codes for organ dysfunction.
The investigators confirmed the findings from the state-based HCUP analysis through inpatient and outpatient Medicare claims during 2008-1014 in a nationally representative sample of 5% of Medicare beneficiaries. These patients had an IRR for seizures of 2.72, and the IRR remained elevated (2.18) relative to patients who were hospitalized with diagnoses other than sepsis even when they excluded patients with ICD-9-CM codes for conditions that confer risk for seizures, including stroke, traumatic brain injury, CNS infection, or brain neoplasm. The seizure outcome in this analysis was defined as one or more inpatient claims for epilepsy or two or more outpatient claims within 3 months of each other.
Since the state-based HCUP data gave a much stronger association between sepsis and subsequent seizures than did the Medicare claims data, the investigators performed a post hoc stratified analysis according to age. Age proved to have a significant effect on the relationship between sepsis and subsequent seizures: Patients aged 65 years or older had an IRR of 2.83, compared with an IRR of 10.33 for those younger than 65.
In an interview, Dr. Reznik said that he sees the results as hypothesis generating and suggested they could serve as a “red flag” for neurologists that’s worth further investigation, given that studies suggest systemic infections and sepsis overall have long-term neurologic implications.
“I think there’s a possibility that, down the line, [sepsis] might be seen as a seizure risk factor, but unfortunately there are limitations from being based on an administrative data set,” he said.
The study was supported by a grant from the National Institute for Neurological Disorders and Stroke to one of the investigators and also by the Michael Goldberg Research Fund. Dr. Reznik had no disclosures to report.