Genotoxic effects of anesthetic agents: an update.

INTRODUCTION: Exposure to anesthetics in the health environment may entail a health risk for patients and operating room personnel. Knowing the effects of anesthetic agents on genetic material could be a valuable basic support for anesthesia care providers to improve treatment performance, increase patient safety and reduce the risks for patients and staff in the operating room. AREAS COVERED: Relevant literature was identified using MEDLINE, CINAHL® and Cochrane Library databases. Over 200 abstracts for articles published from 1980 to 2010 were examined. Original articles were reviewed and relevant citations from these articles were also considered. EXPERT OPINION: Despite some conflicting results, the current available data indicate that exposure to anesthetics, especially nitrous oxide and halogenated agents, is associated with general and genotoxic risks, whereas intravenous agents, such as propofol and its metabolites are not associated with genotoxic effects. Moreover, given that different anesthetic drugs are used in combination it is, thus, very difficult to understand whether the observed effects or absence of effects are due to an individual agent action or linked to a synergy action of different anesthetics involved. Further clinical and experimental evidence is warranted.

Anaesthetic-related neuroprotection: intravenous or inhalational agents?

In designing the anaesthetic plan for patients undergoing surgery, the choice of anaesthetic agent may often appear irrelevant and the best results obtained by the use of a technique or a drug with which the anaesthesia care provider is familiar. Nevertheless, in those surgical procedures (cardiopulmonary bypass, carotid surgery and cerebral aneurysm surgery) and clinical situations (subarachnoid haemorrhage, stroke, brain trauma and post-cardiac arrest resuscitation) where protecting the CNS is a priority, the choice of anaesthetic drug assumes a fundamental role. Treating patients with a neuroprotective agent may be a consideration in improving overall neurological outcome. Therefore, a clear understanding of the relative degree of protection provided by various agents becomes essential in deciding on the most appropriate anaesthetic treatment geared to these objectives. This article surveys the current literature on the effects of the most commonly used anaesthetic drugs (volatile and gaseous inhalation, and intravenous agents) with regard to their role in neuroprotection. A systematic search was performed in the MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINHAL®) and Cochrane Library databases using the following keywords: 'brain' (with the limits 'newborn' or 'infant' or 'child' or 'neonate' or 'neonatal' or 'animals') AND 'neurodegeneration' or 'apoptosis' or 'toxicity' or 'neuroprotection' in combination with individual drug names ('halothane', 'isoflurane', 'desflurane', 'sevoflurane', 'nitrous oxide', 'xenon', 'barbiturates', 'thiopental', 'propofol', 'ketamine'). Over 600 abstracts for articles published from January 1980 to April 2010, including studies in animals, humans and in vitro, were examined, but just over 100 of them were considered and reviewed for quality. Taken as a whole, the available data appear to indicate that anaesthetic drugs such as barbiturates, propofol, xenon and most volatile anaesthetics (halothane, isoflurane, desflurane, sevoflurane) show neuroprotective effects that protect cerebral tissue from adverse events--such as apoptosis, degeneration, inflammation and energy failure--caused by chronic neurodegenerative diseases, ischaemia, stroke or nervous system trauma. Nevertheless, in several studies, the administration of gaseous, volatile and intravenous anaesthetics (especially isoflurane and ketamine) was also associated with dose-dependent and exposure time-dependent neurodegenerative effects in the developing animal brain. At present, available experimental data do not support the selection of any one anaesthetic agent over the others. Furthermore, the relative benefit of one anaesthetic versus another, with regard to neuroprotective potential, is unlikely to form a rational basis for choice. Each drug has some undesirable adverse effects that, together with the patient's medical and surgical history, appear to be decisive in choosing the most suitable anaesthetic agent for a specific situation. Moreover, it is important to highlight that many of the studies in the literature have been conducted in animals or in vitro; hence, results and conclusions of most of them may not be directly applied to the clinical setting. For these reasons, and given the serious implications for public health, we believe that further investigation--geared mainly to clarifying the complex interactions between anaesthetic drug actions and specific mechanisms involved in brain injury, within a setting as close as possible to the clinical situation--is imperative.

Cholinergic central system, Alzheimer's disease, and anesthetics liaison: a vicious circle?

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation and aggregation of amyloid-ß peptide and loss of forebrain cholinergic neurons, resulting in progressive loss of memory and irreversible impairment of higher cognitive functions. Several studies have accounted for the close relationship between AD and the central cholinergic system, suggesting that a dysfunction of acetylcholine containing neurons in the brain contributes significantly to the cognitive deficit of individuals with AD. The aim of the present review is to survey current literature on this topic in order to provide a clear understanding of the role of the cholinergic system in the development and neurodegenerative process of AD. The implications for anesthesia are also discussed. This knowledge could be valuable to improve anesthesia performance and patient safety.

Drugs of anaesthesia and cancer.

Anaesthesia represents one of the most important medical advances in history, and, nowadays, can widely be considered safe, thanks to the discovery of new drugs and the adoption of modern technologies. Nevertheless, anaesthetic practices still represent cause for concern regarding the consequences they produce. Various anaesthetics are frequently used without knowing their effects on specific diseases: despite having been reported that invasion or metastasis of cancer cells easily occurs during surgical procedures, numerous anaesthetics are used for cancer resection even if their effect on the behaviour of cancer cells is unclear. Guidelines for a proper use of anaesthetics in cancer surgery are not available, therefore, the aim of the present review is to survey available up-to-date information on the effects of the most used drugs in anaesthesia (volatile and intravenous anaesthetics, nitrous oxide, opioids, local anaesthetics and neuromuscular blocking drugs) in correlation to cancer. This kind of knowledge could be a basic valuable support to improve anaesthesia performance and patient safety.

Inhaled anesthesia and cognitive performance.

Despite technological advances in surgery and anesthesia during the last few decades, the incidence of postoperative cognitive dysfunction remains a relatively common complication in surgical patients. After surgery, elderly patients in particular often exhibit a transient reversible state of cerebral cognitive alterations. Anesthetics administered as part of a surgical procedure may alter the patient's behavioral state by influencing brain activity. This concise report will address the scientific evidence on the relationship between postoperative cognitive dysfunctions and the most common inhalational agents currently used in anesthesia (volatile anesthetics: isoflurane, desflurane and sevoflurane, gaseous nitrous oxide). The available literature does not allow definitive conclusions to be drawn on the possible differences between anesthetics in relation to the subsequent occurrence of cognitive dysfunction. However, such information is crucial to improve anesthesia performance and patient safety, as well as outcomes.

Pain in Down's syndrome.

Pain is a homeostatic mechanism that intervenes to protect the organism from harmful stimuli that could damage its integrity. It is made up of two components: the sensory-discriminative component, which identifies the provenance and characteristics of the type of pain; and the affective-motivational component, on which emotional reflexes, following the painful sensation, depend. There is a system for pain control at an encephalic and spinal level, principally made up of the periaqueductal grey matter, the periventricular area, the nucleus raphe magnus, and the pain-inhibition complex situated in the posterior horns of the spinal cord. Through the activation of these pain-control systems, the nervous system suppresses the afference of pain signals. Endogenous opioids represent another analgesic system. In the course of various studies on pain transmission in Down patients, the reduced tolerance of pain and the incapacity to give a qualitative and quantitative description emerged in a powerful way. All of these aspects cause difficulty in evaluating pain. This is linked to several learning difficulties. However, it cannot be excluded that in these anomalies of pain perception, both the anatomical and the neurotransmitter alteration, typical of this syndrome, may hold a certain importance. This fact may have important clinical repercussions that could affect the choice of therapeutic and rehabilitative schemes for treatment of pathologies in which pain is the dominant symptom, such as postoperative pain. It could influence research on analgesics that are more suitable for these patients, the evaluation of the depth of analgesia during surgical operation, and ultimately, absence of obvious pain manifestations. In conclusion, alterations of the central nervous system, neurotransmitters, pain transmission, and all related problems should be considered in the management of pain in patients with Down's syndrome, especially by algologists and anesthesiologists.