Association between Physiological Signal Complexity and Outcomes in Moderate and Severe Traumatic Brain Injury: A CENTER-TBI Exploratory Analysis of Multi-Scale Entropy
Frederick A. Zeiler, Ari Ercole, Michał M. Placek, Peter J. Hutchinson, Nino Stocchetti, Marek Czosnyka, Peter Smieleweski, Audny Anke, Ronny Beer, Bo Michael Bellander, Erta Beqiri, Andras Buki, Manuel Cabeleira, Marco Carbonara, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Endre Czeiter, Bart Depreitere, Shirin Frisvold, Raimund Helbok, Stefan Jankowski, Daniel Kondziella, Lars-Owe Koskinen, Ana Kowark, David K. Menon, Geert Meyfroidt, Kirsten Moeller, David Nelson, Anna Piippo-Karjalainen, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Jonathan Rhodes, Saulius Rocka, Rolf Rossaint, Juan Sahuquillo, Oliver Sakowitz, Nina Sundström, Riikka Takala, Tomas Tamosuitis, Olli Tenovuo, Andreas Unterberg, Peter Vajkoczy, Alessia Vargiolu, Rimantas Vilcinis, Stefan Wolf, Alexander Younsi
Abstract
In traumatic brain injury (TBI), preliminary retrospective work on signal entropy suggests an association with global outcome. The goal of this study was to provide multi-center validation of the association between multi-scale entropy (MSE) of cardiovascular and cerebral physiological signals, with six-month outcome. Using the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we selected patients with a minimum of 72 h of physiological recordings and a documented six-month Glasgow Outcome Scale Extended (GOSE) score. The 10-sec summary data for heart rate (HR), mean arterial pressure (MAP), intracranial pressure (ICP), and pulse amplitude of ICP (AMP) were derived across the first 72 h of data. The MSE complexity index (MSE-Ci) was determined for HR, MAP, ICP, and AMP, with the association between MSE and dichotomized six-month outcomes assessed using Mann-Whitney U testing and logistic regression analysis. A total of 160 patients had a minimum of 72 h of recording and a documented outcome. Decreased HR MSE-Ci (7.3 [interquartile range (IQR) 5.4 to 10.2] vs. 5.1 [IQR 3.1 to 7.0]; p = 0.002), lower ICP MSE-Ci (11.2 [IQR 7.5 to 14.2] vs. 7.3 [IQR 6.1 to 11.0]; p = 0.009), and lower AMP MSE-Ci (10.9 [IQR 8.0 to 13.7] vs. 8.7 [IQR 6.6 to 11.0]; p = 0.022), were associated with death. Similarly, lower HR MSE-Ci (8.0 [IQR 6.2 to 10.9] vs. 6.2 [IQR 3.9 to 8.7]; p = 0.003) and lower ICP MSE-Ci (11.4 [IQR 8.6 to 14.4)] vs. 9.2 [IQR 6.0 to 13.5]), were associated with unfavorable outcome. Logistic regression analysis confirmed that lower HR MSE-Ci and ICP MSE-Ci were associated with death and unfavorable outcome at six months. These findings suggest that a reduction in cardiovascular and cerebrovascular system entropy is associated with worse outcomes. Further work in the field of signal complexity in TBI multi-modal monitoring is required.