Anesthetics Provide Limited but Real Protection Against Acute Brain Injury

There are at least two critical stages in acute brain and spinal cord injury. The first is the primary insult, and the second is the tissue’s response to that insult. Both stages can result in persistent morphologic damage and functional disability. To date, the physician can do little to alter these events. This, in part, is due to our limited opportunity to intervene until after the primary damage has occurred. More important, we have only begun to realize how complex neurobiology and pathoneurobiology can be. Our simplistic notions of the nature of neurologic disease, and the body’s response to it, have yet to generate interventions that can meaningfully alter disease progression. Use of unrepresentative preclinical model systems, premature translation of laboratory findings to clinical trials, study of patient populations with a wide spectrum of disease, focus on singular mechanistic events playing out in the vast perturbations of neuronal and glial dysfunction, commercial motivations, and immature clinical trial organizations have contributed to a litany of failures in clinical trials designed to identify meaningful interventions. It is unrealistic to expect any one drug or physiologic management scheme to markedly improve outcome from brain injury across a wide range of patients. This is for two reasons. First, although we would like to consider brain injury a linear event, in fact, it is multiple simultaneous parallel events that may or may not interact with each other. Much like unscrewing a single light bulb in a parallel circuit will not cause the entire system to fail, pharmacologic treatment of a single pathologic event should not be expected to halt other independent events that contribute to injury. Second, commonly encountered disorders such as stroke and traumatic brain injury (TBI) actually represent a spectrum of diseases, often encountered at different stages of progression. Stroke may be hemorrhagic or ischemic. Ischemia may be permanent or temporary, focal or global. TBI may be mechanical or ischemic, diffuse or focal, hemorrhagic or shearing. The type of injury, and the interval after injury at which the physician interacts with it, will define how effective any one therapy can be. Meaningful advance is unlikely to occur until clinical trials can more effectively segregate study patients according to type and stage of disease. Within this context, the effects of anesthetic agents on injured brain are considered. To date, we have little proof that anesthetics reduce morbidity and mortality from acute brain injury in humans. Thus, it is a challenge to argue that these drugs are neuroprotective. At the same time, this can be said of virtually any intervention other than moderate hypothermia applied immediately after resuscitation from out-of-hospital ventricular fibrillation. Not even routinely employed aspects of TBI management including use of mannitol and ventricular drainage have been proven efficacious. Does this mean that anesthetics do not protect? Not necessarily. This could mean that studies appropriately designed to define this protection have not been performed. Until clinical trial designs become sufficiently sophisticated to test this proposition, we must rely on extensive preclinical data and circumstantial human information to support the argument that anesthetics can improve outcome from acute brain injury.