• Critical care medicine · Nov 2015

    Comparative Study Observational Study

    Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis.

    • Zhuo-Hao Liu, Po-Hsun Tu, Nan-Yu Chen, Ping K Yip, Amy L Bowes, Cheng-Chi Lee, She-Hung Chan, Chua-Chi Kung, Alvin Yi-Chou Wang, Chieh-Tsai Wu, and Shih-Tseng Lee.
    • 1Department of Neurosurgery, Chang Gung Memorial Hospital, Chang Gung Medical College and University, Linkou, Taiwan. 2Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. 3Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung Medical College and University, Linkou, Taiwan.
    • Crit. Care Med. 2015 Nov 1;43(11):2416-28.

    ObjectiveThe objective of the present study was to determine whether selective inflammatory cytokine concentrations within cerebrospinal fluid are useful markers for the differential diagnosis of aseptic and bacterial meningitis within neurosurgical patients.DesignProspective, open-label, observational, cohort study.SettingNeurosurgical ICU, Chang Gung Memorial Hospital.PatientsThirty-two consecutive neurosurgical patients who had postoperative fever following external ventricular drain insertion for the treatment of brain injury underwent serial cerebrospinal fluid cytokine analysis pre and post fever to determine the value of such markers in ascertaining the differential diagnosis of meningitis.InterventionCerebrospinal fluid samples were collected on the day of fever onset, as well as on day 2 and 4 pre and post fever development. Tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-8, transforming growth factor-β, and procalcitonin were subsequently analyzed using enzyme-linked immunosorbent assay analysis techniques.Measurement And Main ResultsInflammatory marker levels were compared among febrile aseptic, bacterial, and nonmeningitis patients to determine cerebrospinal fluid inflammatory changes over time. Significant increases in cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, interleukin-6, and interleukin-8 levels were observed within patients with bacterial meningitis at fever onset, which was not evident in aseptic or nonmeningitis patients. Furthermore, significant increases in cerebrospinal fluid tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8 levels were detected as early as 4 days prior to fever onset within patients with bacterial meningitis when compared with both aseptic and nonmeningitis groups. Interestingly, procalcitonin was only significantly increased in patients with bacterial meningitis on the fourth day post fever.ConclusionThe present study suggests that raised cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, and interleukin-8 in a temporal manner may indicate early bacterial meningitis development in neurosurgical patients, enabling earlier diagnostic certainty and improved patient outcomes.

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