Brain Protection in Neurosurgery

Introduction

Neuroprotection describes strategies to protect neuronal elements against damage and impairment of neurologic function. One of the essentials of neuroanesthesia practice is to provide the patient with neuroprotective measures. It is hoped that these measures will reduce poor neurologic outcomes, i.e., motor and sensory deficits and cognitive dysfunction resulting from inevitable surgical brain injury during neurosurgical procedures. The most common forms of brain injury during neurosurgical procedures are (1) brain retraction, (2) incising and removing brain tissue, and (3) temporary vascular occlusion. For instance, eliminating pathological brain tissue and brain retraction will inevitably lead to injury of normal brain structures. Moreover, clamping of a carotid artery during carotid endarterectomy or temporary clipping of intracerebral arteries can simulate unilateral global ischemia or acute ischemic stroke, respectively ( Table 5.1 ).

Neuroprotective strategies can be classified into nonpharmacological and pharmacological ( Table 5.2 ). Some of these strategies are based on laboratory evidence and are either target specific or with indeterminate targets. Other neuroprotective approaches are “empiric” meaning that they are guided by experience not precepts or theory.

Nonpharmacological Strategies

Nonpharmacological strategies signify the manipulation of homeostatic processes in a manner that will have neuroprotective effects ( Table 5.2 ).

Mild Hypothermia

Hypothermia has been commonly classified into three levels: mild from 32 to 35°C, moderate from 32 to 28°C, and deep under 28°C. Deep hypothermia associated with circulatory arrest was previously used during clipping of giant complex intracerebral aneurysms without favorable but detrimental outcomes. Such disappointing experience has steered the evolution of mild hypothermia as a neuroprotective strategy based on encouraging results shown in many laboratory investigations. The mechanisms of the presumed hypothermic neuroprotection are multifaceted and include changes in various cellular processes including its ability to decrease the cerebral metabolic rate by about 10% for every degree Celsius. Hypothermia maintains the integrity of the blood–brain barrier after ischemic insults and constricts cerebral blood vessels and thus reduces brain edema and cerebral blood volume and decreases intracranial pressure (ICP). Additionally, it inhibits excitotoxicity by decreasing glutamate release resulting in decrease of cellular depolarization and inhibition of deleterious calcium influx through voltage- and receptor-operated calcium channels. Also, hypothermia depresses the delayed responses to brain injury, namely reactive oxygen species production and mitochondrial dysfunction that triggers neuronal tissue inflammation and programmed cell death (apoptosis), respectively. Finally, hypothermia can ameliorate secondary neuronal damage by downregulating certain gene-induced proteomic responses leading to cell damage and upregulating a small subset of cold-shock proteins that depress apoptosis and promote cell proliferation.

Despite the various neuroprotective mechanisms of mild hypothermia reported in the laboratory, its clinical efficacy is still indefinable. A recent carefully conducted metaanalysis showed that among patients undergoing craniotomy for various neurosurgical indications including aneurysm clipping, traumatic brain injury, and ischemic stroke there was no evidence that intraoperative or postoperative hypothermia significantly reduces or increases mortality or significantly alters the risk of severe neurologic disability. Application of mild hypothermia did not alter the risk for postoperative complications, i.e., intracranial hemorrhage, ischemic stroke, congestive cardiac failure, or myocardial infarction. There was some weak evidence that postoperative hypothermia may increase the risk of infective complications. Such lack of efficacy and relative safety of mild hypothermia has been in agreement with other systematic reviews. It should be noted that mild hypothermia might be beneficial in the case of comatose survivors of out-of-hospital cardiac arrest and peripartum asphyxia-induced brain injury.

To date, there is no convincing clinical evidence to establish the value of mild hypothermia as a neuroprotective strategy during neurosurgery. Anesthesiologists who opt to use mild hypothermia for their patients because of its favorable safety profile and efficacy in nonneurosurgical situations of global brain ischemia should consider the following precautions: core temperature should be monitored at two sites to avoid inadvertent excessive cooling, target temperature has to be reached before opening the dura, rewarming should start after brain tissue handling has ended, rewarming should continue in the postoperative period until core temperature normalizes, and active cooling equipment should be calibrated and tested before use.