Anesthesia and Neurotoxicity

e16 www.anesthesia-analgesia.org August 2018 • Volume 127 • Number 2 DOI: 10.1213/ANE.0000000000003474 Over 230 million patients undergo anesthesia and surgery annually worldwide. Out of this population, studies suggest that the young and old are both especially vulnerable to harm from anesthetics. Several human epidemiological studies have associated anesthesia administration in early life with the development of learning and behavioral abnormalities in later life. Based on preclinical and epidemiological studies,1–3 the US Food and Drug Administration in 2006 issued a warning that repeated or lengthy use of general anesthetics and sedatives during surgeries or procedures in children <3 years of age or in pregnant women during their third trimester may affect the development of a child’s brain. Additionally, >12% of previously cognitively healthy adult patients undergoing anesthesia and surgery develop shortor long-term postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). Some symptoms such as impaired memory and learning are similar to those in patients with Alzheimer disease, a leading cause of dementia.4,5 POD and POCD can lead to low quality of life, poor prognosis of these patients, and increased personal and social burdens. Anesthetics are frequently cited as a potential cause, supported by epidemiological and animal studies. Furthermore, aging is a risk factor for advanced or long-term cognitive dysfunction after surgery. These findings raise serious concerns regarding the safety of anesthesia use. Patients and parents whose children need surgery are increasingly questioning anesthesiologists regarding this issue. Thus, more literature is needed to help clinicians (eg, anesthesiologists, pediatricians, obstetricians, and surgeons), science researchers, and others (eg, patients and their families) to better understand risks involving anesthetic-induced neurotoxicity, as well as potential protective and therapeutic strategies based on updated research. The following review discusses 1 recently published book that provides important information to various sectors of the medical community. The editor of this book, Dr Morimoto, and other authors are leading Japanese experts in the research field of anesthetic-induced neurotoxicity. Anesthesia and Neurotoxicity has 10 chapters, which are divided into 2 sections. Section 1, “Neurotoxicity of the Anesthetics for Developing Brain,” contains 3 chapters reviewing the evidence of anesthetic-induced neurotoxicity in developing brains based on animal data and clinical findings. The authors also summarize the multiple cellular (apoptosis), subcellular (eg, mitochondria injury), and molecular mechanisms (eg, neurotrophic factors) involved in neurotoxicity, and further discuss prevention and treatment strategies. The authors conclude that (1) contemporary understanding of anesthetic-induced neurotoxicity is mostly derived from animal findings; (2) associations between anesthesia exposure in young patients and adverse neurodevelopmental outcomes have not been ascertained in existing studies. Some epidemiological studies actually have found no correlation between surgery, anesthesia in young patients, and subsequent learning disabilities; and (3) there is a considerable ongoing effort in the form of several large-scale, multicenter prospective clinical studies to fully understand the clinical significance of anesthetic neurotoxicity. Section 2, “Postoperative Delirium and Cognitive Dysfunction,” contains 7 chapters and covers the topics of (1) present clinical status of POD and POCD after both cardiovascular and noncardiac surgeries, (2) diagnosis of POD and POCD, (3) prevention and treatment of POCD, and (4) mechanisms of anesthetic-related POCD. In this section, the authors provide detailed information regarding the incidence rate of POCD, evaluation approaches, risk factors, and management approaches. The underlying POCD mechanisms are multifactorial and largely unknown. In addition, the authors discuss potential mechanisms based on research on identifying cellular, molecular, and neural circuits for the establishment of POD and POCD. This section also emphasizes that, so far, there is no effective treatment option for POD and POCD. However, there are many known ways of mitigating risk, such as through physical exercise. Understanding the risk factors of POCD can help anesthesiologists and surgeons prevent POCD occurrences and implement early treatment of postoperative complications. The table of contents and all chapter materials are also available in PDF format in the electronic version of the book. In conclusion, this book covers a wide range of anesthesia and neurotoxicity topics: from developmental neurotoxicity to POD and POCD, from animal studies to clinical evidence, from diagnosis of neurotoxicity to prevention and treatment approaches, and from symptoms to the underlying mechanisms. Because research efforts in this field are still in their infancy, the authors anticipate future progress in better understanding of the mechanisms and establishment of tools for the screening, prevention, and treatment of POD and POCD.