CSF drain infections: could interleukin-6 (IL-6) be anearly predictor?

AbstractThe University of Manchester. William John Kitchen. 2012.MPhilCSF drain infections: could interleukin-6 be an early predictor?Introduction: External cerebrospinal fluid (CSF) drains are commonly used to temporarily divert CSF flow in patients with hydrocephalus caused by intracranial pathology. Infection is the most common complication of drainage. The definition of infection is the subject of debate and represents a diagnostic challenge but invariably the definition involves analysis of the CSF. A patient who develops a drain related CSF infection does suffer significant morbidity with increased inpatient stays, often in critical care wards. The mortality associated with a drain related infection is less clear, but there are studies describing significant mortality with gram-negative infections. The difficulty in diagnosing drain related infection has led to studies investigating the use of cytokines to aid diagnosis. The use of interleukin-6 (IL-6) in particular has been examined in two studies with inconclusive results. Point of care (POC) devices are commonly used in clinical practice. They generate rapid results which result in immediate therapeutic action. The Picoscan, Milenia Biotech POC device has been used to measure CSF IL-6 in people with subarachnoid haemorrhage. Methods: There are two studies described in this thesis. Firstly, an assessment of a POC device designed to measure CSF IL-6 directly in the laboratory and secondly, a clinical study of patients with hydrocephalus requiring CSF drain insertion. The assessment of the POC device included establishing an external standard curve using known concentrations of IL-6 and the effect of blood on the device. The clinical study was designed to identify whether IL-6 could be used as an early predictor of infection. Samples of CSF were taken daily from patients with external CSF drains and IL-6 concentrations were analysed by Luminex technology. The POC device was also assessed against Luminex technology. Because there is no clear definition of CSF infection in the literature, patient data was reviewed independently by a committee comprised of two consultant neurosurgeons and a consultant microbiologist. They provided an independent clinical diagnosis of CSF infection. Results: The POC device was significantly affected by whole blood and haemolysed blood within the CSF. 8 patients were recruited into the clinical study. The mean age of the patients was 55.6 years. No CSF infections were diagnosed. A Bland-Altman plot of POC IL-6 and Luminex IL-6 was performed which suggests a difference between the two tests that may be clinically significant. Conclusion: More patients need to be recruited to examine whether or not that CSF IL-6 measurement is an accurate method of predicting drain related CSF infection. The POC device, whilst simple to use, is impaired by the presence of whole or haemolysed blood within the CSF. Further tests comparing luminex assay and the POC device need to be performed before the device can be used reliably in the clinical setting.