Deborah Brauser

April 24, 2017

BOSTON — Patients who survive sepsis are at a significantly increased risk for seizures over the long term, new research suggests.

The retrospective cohort study showed a cumulative seizure rate of 6.67% among more than 842,000 patients who were hospitalized for sepsis 8 years earlier vs 1.27% for a matched, general population sample.

Confirmatory analysis using Medicare data showed an incidence rate ratio (IRR) of 2.18 for seizures among patients with sepsis after exclusion of those with stroke, traumatic brain injury, or central nervous system infection/neoplasm.

In addition, sepsis was significantly linked to status epilepticus resulting in hospitalization.

"Our findings support the hypothesis that sepsis could be associated with pathways leading to long-lasting brain injury, independent of other structural lesions," lead author, Michael Reznik, MD, Department of Neurology, Weill Cornell Medicine/Columbia University Medical Center, New York City, told attendees here at the American Academy of Neurology 2017 Annual Meeting (AAN).

Later, session co-moderator Walter Morgan, MD, Florida Hospital, Celebration, told Medscape Medical News that the study was intriguing but he is " interested now in knowing if there's any way we can start to predict these patients."

"If we can figure out how to analyze these cases more thoroughly, and perhaps predict which ones will be more likely to develop seizures down the line, that would be great," said Dr Morgan.

Who Is at Highest Risk?

Dr Reznik noted that common neurologic complications with sepsis include stroke, neuromuscular disease, and sepsis-associated encephalopathy, "which has led to the recognition of long-term cognitive dysfunction after sepsis."

The life-threatening inflammatory response to infection has also been linked previously with short-term risk for seizures.

For the current study, "we wanted to look at these patients and find out if there's a long-term risk of developing seizures after hospital discharge, and, if that is the case, what groups are at the highest risk?" said Dr Reznik.

The investigators assessed discharge claims data from 2005 to 2013 for 842,735 adult patients with sepsis (51% men; 65% white; mean age, 69.2 years) from emergency departments and acute care hospitals in New York, Florida, and California.

As part of the Healthcare Cost and Utilization Project, a personal linkage number is assigned that allows subsequent hospitalizations to be recorded anonymously. None of the patients had seizures before or during their initial hospitalization for sepsis.

The researchers also evaluated a cohort of patients hospitalized for diagnoses other than sepsis who were matched to the sepsis group by age, sex, race, insurance, length of hospital stay and year of hospitalization, discharge location, and presence of organ dysfunction.

In the sepsis group, 30,503 had follow-up seizures; 22.8% of these patients vs 16.2% of those without seizures had "sepsis with neurological dysfunction" at the time of their initial hospitalization.  

Significant Pathways

For the patients with sepsis, the crude rate of seizures after initial hospital discharge was 3.62% (95% confidence interval [CI], 3.58% - 3.66%).

The annual incidence of seizure was 1.29% (95% CI, 1.27% - 1.30%) for the sepsis group vs 0.16% (95% CI, 0.16% - 0.16%) among the three-state general population. In addition, the incidence rate for each of these groups was 1287.9 vs 158.9, respectively, per 100,000 person-years.

While the overall IRR was 4.98 (95% CI, 4.92 - 5.04) for the sepsis survivors vs the general population, the ratio dropped to 4.53 for patients with sepsis and no concurrent neurologic dysfunction — but it rose to 7.52 for those in the sepsis group who did have this type of dysfunction.

The 8-year IRRs for seizures were 7.52 and 4.53, respectively, for patients in the sepsis group with vs without neurologic dysfunction.

Sepsis was also associated with status epilepticus, according to prespecified sensitivity analysis (IRR, 5.42).

Next, the investigators conducted a confirmatory cohort analysis, assessing inpatient and outpatient claims from a 5% sample of Medicare beneficiaries. It showed that "hospitalization for sepsis was again associated with subsequent seizures" (unadjusted IRR, 2.72), reported Dr Reznik.

In a last post hoc subgroup analysis, which stratified by age, the IRRs were 2.83 for the sepsis group who were at least 65 years of age or older (95% CI, 2.78 - 2.88) and 10.33 for those younger than 65 years (95% CI, 10.17 - 10.49).

However, Dr Reznik noted that "this isn't to say that these younger patients are more likely to have seizures than anyone else. The actual incidence is higher in older patients."

The investigators write that the overall findings suggest that "sepsis is associated with pathways that lead to permanent neurological sequelae." Dr Reznik noted that questions going forward include determining risk factors and "Will there be brain-protective strategies on the horizon?"

"Be On the Lookout"

After the presentation, when Dr Reznik was asked whether any familial information was available for the patients, he answered, "No, unfortunately. That would be something great to have in a prospective study."

Dr Morgan later commented that he would be interested to know whether there were any particular exposures to medications, especially antibiotics, in these patients.

"It would be intriguing to know if we could start to look at predictive factors, because it looks like there is obviously an increased risk with these patients developing seizures down the line," he said. "That's something we should be looking out for and something we're missing in the clinical setting."

He added that the issue is important to neurologists and clinicians in other fields, such as primary care. "We need to be on the lookout for this and start asking questions."

The study was supported by a grant from the National Institute of Neurological Disorders and Stroke and by the Michael Goldberg Research Fund. Dr Reznik and Dr Morgan have disclosed no relevant financial relationships.

American Academy of Neurology 2017 Annual Meeting (AAN). Emerging Science abstract S5.003. Presented April 23, 2017.

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