Stephan Mayer, M.D.

Funded in September 2005: $200,000 for 2 years

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Neurological Intensive Care Unit Multimodal Monitoring Project

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Neurological Intensive Care Unit Multimodal Monitoring Project

Neurocritical care is a specialty that focuses on the critical care management of patients with catastrophic neurologic diseases such as traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage. Traditionally, neuromonitoring is based on a "reactive" model, in which abnormal physiology or neurological deterioration is detected, which then triggers corrective actions to reverse this process. Multimodality monitoring refers to the tracking of multiple parameters of brain physiology and function that can be affected by direct medical or surgical intervention.

We propose a novel paradigm to assess the pathophysiological events that accompany acute hemorrhagic stroke by combining the use of emerging neuromonitoring modalities in a Neuro-ICU. The overall vision of this project is to establish a new therapeutic paradigm in which multimodality neuromonitoring is used to provide real-time feedback, allowing the clinician to optimize systemic physiology, thus creating an optimal cellular environment that will both preserve neurologic function and allow the best chance for recovery to occur.

The specific goals of this project are: 1) To create software tools for the bedside that enable physicians to evaluate relationships between systemic physiological variables and indicators of neuronal health in real time; 2) To determine if two brain tissue measures of neuronal oxidative stress—oxygen tension and lactate/pyruvate ratio—can be optimized by the manipulation of systemic physiological variables such as blood pressure, osmolality, and temperature in patients with hemorrhagic stroke; 3) To determine whether the extent and duration of neuronal oxidative stress and physiological derangement is predictive of long term clinical and functional outcome after hemorrhagic stroke.

The ultimate goal of this project was to create a stable, robust, and user-friendly data acquisition and analysis system for studying brain multimodality monitoring (MMM) data in comatose patients with severe brain injury. At the time of this final report, we have formally launched a live real-time bedside multimodality monitoring system in all 18 of our neuro-ICU beds as of December 2006.  Further, we have begun development and characterization of a novel paradigm for the graphical interpretation of bedside physiological data, which can be used to optimize key physiological drivers such as cerebral perfusion pressure (CPP) and end-tidal CO2. Finally, we have successfully started enrollment in an outcomes assessment program approved by our Institutional Review Board (IRB).

Support from the Charles A. Dana Foundation has allowed us to address a significant unmet need in the clinical neurosciences, and has served as a building block toward the ultimate goal of developing a data management system that can be used in neurological intensive care units throughout the world. Over the two-year funding period we collected over 2,500 hours of multimodal ICU data on 29 patients, presented data at four international scientific conferences, and prepared two manuscripts, focusing on the use of PbtO2 reactivity for evaluating cerebrovascular auto regulation after brain injury, and our initial observations of a powerful relationship between falling brain tissue glucose levels and failure to recover from coma. Finally, infrastructure development made possible by the Dana Foundation has led to a successful 5-year NIH training grant (K12) award to Dr. Neeraj Badjatia, who will be investigating the effects of therapeutic hypothermia modulation on brain oxygenation and metabolism, and has provided crucial preliminary data for 2 additional NIH grant applications—a K12/K23 application by Dr. Schmidt and a R01 application by Dr. Mayer—that will be submitted in 2008.

Support from the Dana Foundation has also allowed us to develop novel analytic systems for understanding complex MMM physiological data in new ways.  We have made several important discoveries during the funding period.  With continuous analysis of brain tissue oxygen tension (PbtO2) we developed a novel method of graphical analysis for guiding goal-directed therapy based on brain tissue oxygen targets system that can detect paroxysmal episodes of auto-regulatory failure in the comatose injured brain.  We also developed a correlating graphical analysis system that can use PbtO2 and intracranial pressure (ICP) data to identify optimized cerebral perfusion pressure (CPP) targets, thus optimizing brain perfusion while minimizing the risk of brain edema.  In addition, we identified critical reductions in brain glucose levels as a potentially important marker of metabolic brain failure in coma. Moreover, we found that the widely-used management strategy of intensive insulin therapy—a practice that has been validated in surgical (not neurological) ICU patients—may aggravate brain tissue hypoglycemia and cause harm to brain-injured patients. The latter discovery was selected as a prizewinner as one of the best scientific abstracts at the recent Society of Critical Care Medicine Meeting in Honolulu, HI.

Collectively, these insights promise to have a major impact on the way that comatose brain-injured patients are managed in the ICU setting, and ultimately to improve the chances of survival and good recovery in this critically injured patient population.

Stephan Mayer, M.D.

Stephan A. Mayer, M.D., is Associate Professor of Clinical Neurology and Neurosurgery at Columbia University and Director of the Neurological Intensive Care Unit at New York-Presbyterian Hospital at Columbia. He earned his bachelor's degree from Brown University and his medical degree from Cornell University Medical College. He then went on to do his postdoctoral clinical training in neurology and neurological intensive care at the Neurological Institute of New York and Columbia University Medical Center.

Dr Mayer's research interests include subarachnoid and intracerebral hemorrhage, therapeutic hypothermia, status epiliepticus, and neurological outcomes assessment. He is principal investigator of the Factor VIIa in Acute Hemorrhagic Stroke Trial (FAST) and Director of the Columbia University Subarachnoid Hemorrhage Outcomes Project. Dr Mayer is Treasurer of the Neurocritical Care Society, co-founder and associate editor of the journal Neurocritical Care, and a co-author of Ropper's textbook on Neurological and Neurosurgical Intensive Care.