Clark-Clermont Team Awarded NIH R21 Grant to Study Real-time Assessment of Intracranial Compliance

Professors Robert Clark, MD and Gilles Clermont, MD have been awarded a two-year, Multiple Principal Investigators Exploratory Neuroscience Research Grant (R21) from the National Institute of Neurological Disorders and Stroke. The study is entitled “Innovative Methods for Real-time Assessment of Intracranial Compliance.”

The Clark-Clermont team will investigate the validity of an algorithm to compute dynamic intracranial compliance in real-time for patients with severe traumatic brain injury (TBI), which is a leading cause of death and long-term neurological impairment in children and adults. Pitt assistant professor of Industrial Engineering Hyo Kyung Lee, PhD is a collaborator on the project, along with CCM faculty members Pat Kochanek, MD and Chris Horvat, MD. The team also includes PCCM fellow Jay Rakkar, MD and former PCCM fellow Michael Wolf, MD.

“For decades, the standard of care has not changed for neurological monitoring of TBI patients,” said Dr. Clark, who is a professor of Critical Care Medicine and Pediatrics and the vice chair for Pediatric Critical Care in the Department of Critical Care Medicine. “TBI care has relied mainly on intracranial pressure (ICP) monitoring. Yet remarkably, the use of ICP alone as a therapeutic target for severe TBI is currently controversial due to a lack of robust supporting evidence, especially for its use in children.”

To address this clinical need, the Clark-Clermont team developed the ICP-PCO2 Compliance Index (PCI) algorithm that integrates continuous ICP and end tidal CO(ETCO2) data streams. 

The PCI algorithm is based on the well-known and robust relationship between the partial pressure of CO2 in blood (PCO2), cerebrovascular reactivity, and cerebral blood volume (CBV). With normal intracranial compliance ETCO2 and ICP are completely uncoupled. With abnormal intracranial compliance as seen after severe TBI, fluctuations in ETCO2 typically seen during the course of routine ICU care produce changes in CBV and immediate changes in ICP, as reflected in the PCI.

“We are tapping into the availability of continuous ICP and ETCOmonitoring, both of which are standard of care for patients with severe TBI,” explained Dr. Clermont, professor of Critical Care Medicine, Mathematics, Clinical and Translational Science, and Industrial Engineering; director of the CRISMA Program on Systems Medicine; and medical director of the Center for Inflammation and Regenerative Modeling at the University of Pittsburgh. “Our ICP-PCO2 Compliance Index can be determined using these existing ICU monitoring tools.”

Successful validation of the ICP-PCO2 Compliance Index will lay the groundwork for the development of a valuable clinical tool for all centers managing children and adults with severe TBI; and can be readily integrated and implemented in ICUs.