Perioperative cerebral damage can result in various clinical sequela ranging from minor neurocognitive deficits to catastrophic neurological morbidity with permanent impairment and death. The goal of neuroprotective treatments is to reduce the clinical effects of cerebral damage through two major mechanisms: increased tolerance of neurological tissue to ischemia and changes in intra-cellular responses to energy supply deprivation. In this review, we present the clinical evidence of intravenous anesthetics on perioperative neuroprotection, and we also provide a critical perspective for future studies. The neuroprotective efficacy of the intravenous anesthetics thiopental, propofol and etomidate is unproven. Lidocaine may be neuroprotective in non-diabetic patients who have undergoing cardiac surgery with cardiopulmonary bypass (CBP) or with a 48-hour infusion, but conclusive data are lacking. There are several limitations of clinical studies that evaluate postoperative cognitive dysfunction (POCD), including difficulties in identifying patients at high-risk and a lack of consensus for defining the "gold-standard" neuropsychological testing. Although a battery of neurocognitive tests remains the primary method for diagnosing POCD, recent evidence suggests a role for novelbiomarkers and neuroimaging to preemptively identify patients more susceptible to cognitive decline in the perioperative period. Current evidence, while inconclusive, suggest that intravenous anesthetics may be both neuroprotective and neurotoxic in the perioperative period. A critical analysis on data recorded from randomized control trials (RCTs) is essential in identifying patients who may benefit or be harmed by a particular anesthetic. RCTs will also contribute to defining methodologies for future studies on the neuroprotective effects of intravenous anesthetics.
Perioperative cerebral damage may be associated with surgery and anaesthesia. Pharmacological perioperative neuroprotection is associated with conflicting results. In this qualitative review of randomized controlled clinical trials on perioperative pharmacological brain neuroprotection, we report the effects of tested therapies on new postoperative neurological deficit, postoperative cognitive decline (POCD), and mortality rate. Studies were identified from Cochrane Central Register and MEDLINE and by hand-searching. Of 5904 retrieved studies, 25 randomized trials met our inclusion criteria. Tested therapies were: lidocaine, thiopental, S(+)-ketamine, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate and xenon remacemide, atorvastatin, magnesium sulphate, erythropoietin, piracetam, rivastigmine, pegorgotein, and 17β-estradiol. The use of atorvastatin and magnesium sulphate was associated with a lower incidence of new postoperative neurological deficit. The use of lidocaine, ketamine, and magnesium sulphate was associated with controversial results on POCD. The POCD did not differ between treated patients and control group for other tested drugs (thiopental, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate, xenon, erythropoietin, remacemide, piracetam, rivastigmine, pegorgotein, and 17β-estradiol). None of the tested drugs was associated with a reduction in mortality rate. Drugs with various mechanisms of action have been tested over time; current evidence suggests that pharmacological brain neuroprotection might reduce the incidence of new postoperative neurological deficits and POCD, while no benefits on perioperative mortality are described. Of importance from this review is the need for shared methodological approach when clinical studies on pharmacological neuroprotection are designed.