LAUSR

Introduction/Hypothesis: A subset of patients with severe sepsis is recognized to have pathologic immune system activation. Specific inflammation phenotypes are associated with greater mortality. Recent studies have shown improved outcomes of patients with hyperferritinemic sepsis after treatment with an IL-1 receptor antagonist (anakinra). The objective of this study was to describe a single pediatric intensive care unit’s (PICU) experience with the use of anakinra in children with suspected sepsis and signs of hyperinflammation. Methods: We conducted a retrospective study of patients admitted to a tertiary referral PICU from 2015 to 2018. We included patients given anakinra for suspected sepsis with hyperinflammation. We excluded patients previously started on anakinra during the same hospital admission, with hyperinflammation unrelated to infection, and subsequently diagnosed with primary HLH. We collected data on clinical characteristics, laboratory/microbiologic data, treatments, and outcomes. Results: Thirty-two admissions were included; mean age was 7.8 years. Median PRISM III-based risk of mortality was 6.8%. Thirteen of 32 patients (41%) were previously healthy while 19 (59%) had chronic comorbid conditions, most commonly cancer (7/32, 22%). Majority (23/32, 72%) developed multiorgan dysfunction with 72% on mechanical ventilation, 38% requiring vasoactive infusions, and 19% needing extra-corporeal support. Majority (72%) fulfilled >3 of 8 HLH criteria. Anakinra was initiated a median of 1 day after PICU admission with 97% given intravenously. Median maximum doses were 20 mg/kg/day (<40 kg) and 916 mg/day (>40 kg). Other immunomodulatory therapies included: IVIG (78%), methylprednisolone (69%), hydrocortisone (63%), and plasmapheresis (13%). Vasoactive-inotropic scores decreased by 24% from the 1st to the 3rd day after anakinra initiation. Biochemical parameters decreased from baseline to the 7th day after anakinra initiation as follows: median ferritin by 67% from 5059 to 1659 ng/mL and median CRP by 78% from 5.5 to 1.2 mg/dL. No infections were attributed to anakinra therapy. Fourteen of 32 patients (44%) died before hospital discharge. Conclusions: The use of an interleukin-1 receptor antagonist for specific sepsis inflammation phenotypes is a promising treatment modality and requires further study.