Predictive Value of Intrathecal Interleukin-6 for Ventriculostomy-related Infection

 

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Abstract

Background and Study Aim: Early diagnosis of ventriculostomy-related infection (VRI) is crucial for the early treatment and course of this disease. In neurosurgical patients the diagnostic criteria are equivocal, mostly because of bloodstained cerebrospinal fluid (CSF). The predictive value, sensitivity and specificity of intrathecal interleukin-6 (IL-6_CSF) has been proven for VRI compared with classical diagnostic CSF parameters, i.e. cell countCSF (CC_CSF) and total protein_CSF.

Patients and Methods: We prospectively analyzed the daily clinical data and CSF samples of 75 neurosurgical patients with an external ventricular drainage (EVD), which had been inserted predominantly because of poor-grade subarachnoid hemorrhage (SAH). The intrathecal interleukin-6 concentrations (IL-6_CSF) were correlated with the clinical course and VRI incidence, as diagnosed by the classical VRI criteria (CC_CSF, total protein_CSF, clinical symptoms).

Results: Based on classical criteria, bacterial meningitis occurred in 26.7% of patients. Patients with VRI manifested significantly (p<0.001) higher median values of IL-6_CSF (up to 2000-fold increase) the day before (day -1) infection was diagnosed by conventional parameters. Using a cut-off value of IL-6_CSF≥2700 pg/ml [4050 pg/ml after WHO standardization] on day -1, the relative risk for VRI was 6.09 (95% CI: 2.62-14.18%). A predictive value of IL-6_CSF≥2700 pg/ml [4050 pg/ml] for VRI was calculated of 89% (95% CI: 79.6-98.0%), a sensitivity of 73.7% and a specificity of 91.4%. The amount of intrathecal blood was an independent risk factor for VRI occurrence, whereas the mean duration of EVD in place showed no impact on the rate of infection.

Conclusion: Our data indicate that IL-6_CSF is a reliable marker for predicting VRI prior to clinically manifest meningitis, one day earlier than the common diagnostic criteria of CSF infection (CC_CSF, total protein _CSF, clinical symptoms).

Zusammenfassung

Einleitung: Die frühe Diagnosestellung einer Ventrikulostomie-assoziierten Infektion (VAI) ist von entscheidender Bedeutung für die Therapieeinleitung und damit dem weiteren Verlauf der Erkrankung. Im neurochirurgischen Patientengut sind die Kriterien zur Diagnosesicherung auf Grund der häufig blutigen Veränderung des Liquors unsicher. Ziel dieser Studie ist es, den Vorhersagewert für das Vorliegen einer VAI anhand von intrathekalem IL-6 (IL-6_CSF) sowie die diesbezügliche Sensitivität und Spezifität zu untersuchen und mit den klassischen Liquorparametern Zellzahl (CC_CSF) und Gesamteiweiß zu vergleichen.

Patienten und Methodik: Wir analysierten prospektiv tägliche klinische Parameter und Liquorproben von 75 konsekutiven neurochirurgischen Patienten mit externen Ventrikeldrainagen (EVD), deren Anlage zum überwiegenden Anteil auf Grund einer schweren Subarachnoidalblutung indiziert war. Die Konzentration des IL-6_CSF wurde mit dem klinischen Verlauf und mit der Rate an VAI, die mit den klassischen Kriterien diagnostiziert worden waren (klinische Symptome, CC_CSF, Gesamteiweiß_CSF) korreliert.

Ergebnisse: Bei 26.7% der Patienten kam es zum Auftreten einer VAI. Patienten, die eine VAI entwickelten wiesen am Tag vor Diagnosestellung (Tag -1) signifikant höhere (p<0.001) IL-6_CSF-Werte auf. Unter Zugrundelegung eines cut-off Wertes des IL-6_CSF>2700 pg/ml [4050 pg/ml] am Tag-1 ergab sich für das Vorliegen einer VAI ein 6.09-fach höheres Risiko (95% CI: 2.62-14.18%). Der Vorhersagewert für IL-6_CSF>2700 pg/ml [4050 pg/ml] für VAI lag bei 89% (95% CI: 79.6-98.0%), die Sensitivität bei 73.7%, die Spezifität bei 91.4%. Das Ausmaß an intrathekalem Blut war ein unabhängiger Risikofaktor für die Entwicklung einer VAI, wohingegen die Dauer der EVD keinen Einfluss auf die Rate an VAI hatte.

Schlussfolgerung: Unsere Daten weisen darauf hin, dass IL-6_CSF als wichtiger Vorhersagemarker für das Vorliegen einer VAI anzusehen ist; und dies ist bereits einen Tag vor Änderungen der konventionellen diagnostischen Parameter (CC_CSF, Gesamteiweiß_CSF, klinische Symptome) festzustellen.

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Correspondence

B. SchochMD 

Department of Neurosurgery

University Hospital

Hufelandstr. 55

45147 Essen

Germany

Phone: +49/291/723 12 37

Fax: +49/291/723 12 41

Email: beate.schoch@uk-essen.de