Use of Clustering to Investigate Changes in Intracranial Pressure Waveform Morphology in Patients with Ventriculitis.

Abstract

This study aimed to examine whether changes in intracranial pressure (ICP) waveform morphologies can be used as a biomarker for early detection of ventriculitis. Consecutive patients (N=1653) were prospectively enrolled in a hemorrhage outcomes study from 2006 to 2018. Of these, 435 patients (26%) required external ventricular drains (EVDs) and 76 (17.5% of those with EVDs) had ventriculitis treated with antibiotics. Nineteen patients (25% of those with ventriculitis) showed culture-positive cerebrospinal fluid (CSF) and were included in the present analysis. CSF was routinely cultured three times per week and additionally if infection was suspected. EVDs were left open for drainage, with ICP assessed hourly by clamping. Using wavelet analysis, we extracted uninterrupted segments of ICP waveforms. We extracted dominant pulses from continuous high-resolution data, using morphological clustering analysis of intracranial pressure (MOCAIP). Then we applied k-means clustering, using the dynamic time warping distance to obtain morphologically similar groupings. Finally, metaclusters and further-split clusters (when equipoise existed) were categorized for broad comparison by clinician consensus. We extracted 275,911 dominant pulses from 459.9h of EVD data. Of these, 112,898 pulses (40.9%) occurred before culture positivity, 41,300 pulses (15.0%) occurred during culture positivity, and 121,713 pulses (44.1%) occurred after it. K-means identified 20 clusters, which were further grouped into metaclusters: tri-/biphasic, single-peak, and artifactual waveforms. Prior to ventriculitis, 61.8% of dominant pulses were tri-/biphasic; this percentage reduced to 22.6% during ventriculitis and 28.4% after it (p<0.0001). One day before the first positive cultures were collected, the distribution of metaclusters changed to include more single-peak and artifactual ICP waveforms (p<0.0001). The distribution of ICP waveform morphology changes significantly prior to clinical diagnosis of ventriculitis and may be a potential biomarker.