TY - JOUR
T1 - Relationship Between RAP and Multi-Modal Cerebral Physiological Dynamics in Moderate/Severe Acute Traumatic Neural Injury
T2 - A CAHR-TBI Multivariate Analysis
AU - Islam, Abrar
AU - Stein, Kevin Y
AU - Griesdale, Donald
AU - Sekhon, Mypinder
AU - Raj, Rahul
AU - Bernard, Francis
AU - Gallagher, Clare
AU - Thelin, Eric P
AU - Mathieu, Francois
AU - Kramer, Andreas
AU - Aries, Marcel
AU - Froese, Logan
AU - Zeiler, Frederick A
PY - 2025/9/22
Y1 - 2025/9/22
N2 - BACKGROUND: The cerebral compliance (or compensatory reserve) index, RAP, is a critical yet underutilized physiological marker in the management of moderate-to-severe traumatic brain injury (TBI). While RAP offers promise as a continuous bedside metric, its broader cerebral physiological context remains partly understood. This study aims to characterize the burden of impaired RAP in relation to other key components of cerebral physiology. METHODS: Archived data from 379 moderate-to-severe TBI patients were analyzed using descriptive and threshold-based methods across three RAP states (impaired, intact/transitional, and exhausted). Agglomerative hierarchical clustering, principal component analysis, and kernel-based clustering were applied to explore multivariate covariance structures. Then, high-frequency temporal analyses, including vector autoregressive integrated moving average impulse response functions (VARIMA IRF), cross-correlation, and Granger causality, were performed to assess dynamic coupling between RAP and other physiological signals. RESULTS: Impaired and exhausted RAP states were associated with elevated intracranial pressure ( = 0.021). Regarding AMP, impaired RAP was associated with elevated levels, while exhausted RAP was associated with reduced pulse amplitude ( = 3.94 × 10 ). These two RAP states were also associated with compromised autoregulation and diminished perfusion. Clustering analyses consistently grouped RAP with its constituent signals (ICP and AMP), followed by brain oxygenation parameters (brain tissue oxygenation (PbtO ) and regional cerebral oxygen saturation (rSO )). Cerebral autoregulation (CA) indices clustered more closely with RAP under impaired autoregulatory states. Temporal analyses revealed that RAP exhibited comparatively stronger responses to ICP and arterial blood pressure (ABP) at 1-min resolution. Moreover, when comparing ICP-derived and near-infrared spectroscopy (NIRS)-derived CA indices, they clustered more closely to RAP, and RAP demonstrated greater sensitivity to changes in these ICP-derived CA indices in high-frequency temporal analyses. These trends remained consistent at lower temporal resolutions as well. CONCLUSION: RAP relationships with other parameters remain consistent and differ meaningfully across compliance states. Integrating RAP into patient trajectory modelling and developing predictive frameworks based on these findings across different RAP states can map the evolution of cerebral physiology over time. This approach may improve prognostication and guide individualized interventions in TBI management. Therefore, these findings support RAP's potential as a valuable metric for bedside monitoring and its prospective role in guiding patient trajectory modeling and interventional studies in TBI.
AB - BACKGROUND: The cerebral compliance (or compensatory reserve) index, RAP, is a critical yet underutilized physiological marker in the management of moderate-to-severe traumatic brain injury (TBI). While RAP offers promise as a continuous bedside metric, its broader cerebral physiological context remains partly understood. This study aims to characterize the burden of impaired RAP in relation to other key components of cerebral physiology. METHODS: Archived data from 379 moderate-to-severe TBI patients were analyzed using descriptive and threshold-based methods across three RAP states (impaired, intact/transitional, and exhausted). Agglomerative hierarchical clustering, principal component analysis, and kernel-based clustering were applied to explore multivariate covariance structures. Then, high-frequency temporal analyses, including vector autoregressive integrated moving average impulse response functions (VARIMA IRF), cross-correlation, and Granger causality, were performed to assess dynamic coupling between RAP and other physiological signals. RESULTS: Impaired and exhausted RAP states were associated with elevated intracranial pressure ( = 0.021). Regarding AMP, impaired RAP was associated with elevated levels, while exhausted RAP was associated with reduced pulse amplitude ( = 3.94 × 10 ). These two RAP states were also associated with compromised autoregulation and diminished perfusion. Clustering analyses consistently grouped RAP with its constituent signals (ICP and AMP), followed by brain oxygenation parameters (brain tissue oxygenation (PbtO ) and regional cerebral oxygen saturation (rSO )). Cerebral autoregulation (CA) indices clustered more closely with RAP under impaired autoregulatory states. Temporal analyses revealed that RAP exhibited comparatively stronger responses to ICP and arterial blood pressure (ABP) at 1-min resolution. Moreover, when comparing ICP-derived and near-infrared spectroscopy (NIRS)-derived CA indices, they clustered more closely to RAP, and RAP demonstrated greater sensitivity to changes in these ICP-derived CA indices in high-frequency temporal analyses. These trends remained consistent at lower temporal resolutions as well. CONCLUSION: RAP relationships with other parameters remain consistent and differ meaningfully across compliance states. Integrating RAP into patient trajectory modelling and developing predictive frameworks based on these findings across different RAP states can map the evolution of cerebral physiology over time. This approach may improve prognostication and guide individualized interventions in TBI management. Therefore, these findings support RAP's potential as a valuable metric for bedside monitoring and its prospective role in guiding patient trajectory modeling and interventional studies in TBI.
KW - RAP
KW - cerebral compliance
KW - cerebral physiology
KW - multimodal monitoring
KW - traumatic brain injury
U2 - 10.3390/bioengineering12091006
DO - 10.3390/bioengineering12091006
M3 - Article
SN - 2306-5354
VL - 12
JO - Bioengineering
JF - Bioengineering
IS - 9
M1 - 1006
ER -