Assessing Outcomes of Interventions Based on Brain Monitoring of Comatose Patients
Stephan Mayer, M.D.
New York - Presbyterian Hospital
Clinical Neuroscience Research
March 2009, for 3 years
Assessing outcomes of interventions based on brain monitoring of comatose patients
This study will begin to determine whether intensive care interventions that are undertaken in comatose brain-injured patients in response to several interrelated physiologic and metabolic factors that are constantly monitored in the brain are correlated with improved functional outcomes in the patients during their recovery. If so, the research will lead to expanded clinical research to develop optimal, patient-specific acute brain therapy. The acute care provided in intensive care units (ICUs) immediately after catastrophic brain injury can mean the difference between life and death and—for those who survive—between functional or dysfunctional lives. Such injuries include “hemorrhagic” stroke (called intracerebral hemorrhage), which is produced when a blood vessel in the brain bursts, usually resulting from high blood pressure. The blood irritates the surrounding brain tissue, producing potentially deadly brain swelling. Another condition is “subarachnoid hemorrhage,” which is produced when a weakened part of a blood vessel in a membrane covering the brain bursts (called an aneurism). This event can cause nearby blood vessels to contract, robbing brain cells of vital oxygen and nutrients and causing cells to die. Brain oxygen and glucose are essential for survival: the brain receives approximately 15 percent of blood pumped by the heart and consumes 20 percent of the oxygen and 25 percent of the glucose (sugar) available to the entire body.
Until recently, ICU doctors identified adverse effects in progress and reacted with clinical interventions to limit damage. Within the last few years, however, a number of technological advances have enabled critical care physicians to directly monitor multiple factors affecting the physiology and function of an acutely injured brain. At the forefront of these efforts is a team of New York Presbyterian Hospital investigators. Through a probe inserted through the skull into the brain of comatose head-injured patients, they continuously monitor a host of factors involved in the brain’s oxygenation and metabolism, with measures graphically displayed on a computer screen. Their initial studies, funded in part by Dana, suggest that the most important of these are measures of cerebral blood flow, brain tissue oxygen, and blood sugar levels (oxidative metabolism) in the brain. Preliminary research indicates that interventions normalizing these measures correlate with survival and good functional recovery.
The team now proposes to study the role of individual and combined factors in patients’ “acute phase” and relate these to patients’ recovery outcomes. Specifically, they plan to: 1) measure additional physiologic factors, and characterize the effect of specific ICU interventions on brain function and metabolism during the acute phase; and 2) assess patients’ functional outcomes. They will study up to 40 adult brain-injured patients throughout the acute and recovery phases over a period of two years. During the recovery period, they will conduct telephone interviews following hospital discharge at two weeks, three months, and one year to assess global cognitive functioning and disability/ability in everyday functions. Additionally, they will collaborate with investigators at three other centers that also use multimodal monitoring (University of California at Los Angeles and San Francisco, and the University of Pennsylvania) to pool data to correlate acute and recovery phase results.
Multi-Modality Monitoring of Acute Brain Injury
Neurocritical care is a specialty that focuses on promoting the support and recovery of patients with catastrophic neurologic diseases such as traumatic brain injury, subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). Multimodality monitoring refers to the recording and analysis of various measures of brain physiology and function that can be affected by direct medical or surgical intervention. In the past, monitoring in the neurologic intensive care unit was restricted to clinical examination; basic aspects of heart and lung function (such as heart and respiratory rate, oxygen saturation, and blood pressure); and intracranial pressure (ICP). Today a number of newer advanced technologies can now allow physicians to intensively monitor the physiology and function of the acutely-injured brain. These modalities include cerebral blood flow, brain tissue oxygen tension, depth EEG, and brain tissue glucose, lactate, and pyruvate, which can be measured with microdialysis.
In contrast to older reactive models of ICU monitoring, our vision is to use advanced neuromonitoring in a proactive fashion in order to establish and maintain an optimal physiological environment for the comatose injured brain.
Aim 1 is to study the impact of basic systemic physiologic abnormalities (involving blood pressure, hemoglobin, glucose, ETCO2, and temperature) on cerebral metabolism and brain oxygen tension.
Aim 2 is to characterize the impact of common ICU interventions (including intravenous sedation, ventilator weaning, osmotherapy with mannitol or hypertonic saline, and blood transfusion) on cerebral metabolism and brain oxygen tension.
Aim 3 is to ascertain the relationship between brain physiologic markers and long-term functional and cognitive outcome.
The experimental paradigm that we propose consists of integrating physiologic and metabolic assessment of neuronal function during the critical phase of brain injury with rigorously-measured patient-centered clinical outcomes during the recovery phase. Our idea is that outcome following critical brain injury, as measured by several disability scales, is highly dependent on neuronal events occurring during the acute phase. With support from the Dana Foundation we will build on our existing database and (1) continue to determine how systemic physiologic parameters and common ICU interventions impact on brain metabolism and physiology, and (2) develop a complete follow-up protocol of all clinical events during the recovery phase to better understand the relationship between deranged brain physiology and functional outcome. The study we propose here is a prospective longitudinal cohort study designed to collect repeated measures of neuronal function after brain injury and repeated measures of neurological outcome chronically throughout the disease. Our ultimate goal is to use real-time graphical analysis of multimodality data to individualize physiologic brain support based on the principle of goal-directed therapy – such as maintaining optimized brain tissue oxygenation and oxidative metabolism.
Stephan Mayer, M.D.
Stephan A. Mayer, MD, is Professor of Clinical Neurology and Neurological Surgery at Columbia University College of Physicians & Surgeons in New York City, and is Director of the Neurological Intensive Care Unit at Columbia University Medical Center. He is a graduate of Brown University, received his medical degree from Cornell University Medical College in New York, and did his postgraduate medical training in neurology and neurological intensive care at the Neurological Institute of New York.
Dr. Mayer is considered a world leader in the field of neurological intensive care. He has published more than 250 journal articles, books, case reports, book chapters, and abstracts. He is principal investigator of the NovoSeven ICH Trial, a worldwide multicenter clinical trial evaluating ultra-early hemsotatic therapy for brain hemorrhages, and is director of the Columbia University Subarachnoid Hemorrhage Outcomes Project, an AHA-funded study designed to identify novel risk factors for neurocognitive impairment in patients with brain aneurysms. Dr. Mayer is also active in research related to therapeutic hypothermia, neurocardiac injury, status epilepticus, and cerebral blood flow monitoring. He is the recipient of many awards, including the Society of Critical Care Medicine 2003 Neuroscience Award.
Dr. Mayer is a founding member of the Neurocritical Care Society, and is associate editor of the journal Neurocritical Care. He is a co-author of several textbooks, including Therapeutic Hypothermia and Neurological and Neurosurgical Intensive Care, which is considered the standard text in the field. His work as a neurointensivist was also recently profiled in the book Back From the Brink, which describes how technological advances in intensive care medicine have led to dramatic improvements in outcome after brain injury.