[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · May 2011 · Expert Opinion on Drug Safety
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: With longevity, postoperative cognitive decline in the elderly has emerged as a major health concern for which several factors have been implicated, one of the most recent being the role of anaesthetics. Interactions of anaesthetic agents and different targets have been studied at the molecular, cellular and structural anatomical levels. Recent in vitro nuclear magnetic resonance spectroscopy studies have shown that several anaesthetics act on the oligomerisation of amyloid beta peptide. Uncontrolled production, oligomerisation and deposition of amyloid beta peptide, with subsequent development of amyloid plaques, are fundamental steps in the generation of Alzheimer's disease. Amyloid beta peptide is naturally present in the central nervous system, and is found at higher tissue concentrations in the elderly. We argue that administering certain general anaesthetics to elderly patients may worsen amyloid beta peptide oligomerisation and deposition and thus increase the risk of developing postoperative cognitive dysfunction. The aim of this review is to highlight the clinical aspects of postoperative cognitive dysfunction and to find plausible links between possible anaesthetic effects and the molecular pathological mechanism of Alzheimer's disease. It is hoped that our hypothesis will stimulate further enquiry, especially triggering research into elucidating those anaesthetics that may be more suitable when cognitive dysfunction is a particular concern.
[Show abstract][Hide abstract] ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation and aggregation of amyloid-β 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.
Full-text · Article · Jan 2010 · Journal of Alzheimer's disease: JAD
[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · May 2009 · Surgical Oncology
[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · Feb 2009 · Drugs of today (Barcelona, Spain: 1998)
[Show abstract][Hide abstract] ABSTRACT: Preliminary research results indicate that exposure to anesthetics affects health.
To provide, with evidence-based knowledge, the answer to the question: What are the genotoxic effects threatening people exposed to anesthetics?
A systematic review of scientific literature. A systematic search of The Cochrane Library, MedLine, and CINAHL resulted in a screening of 212 abstracts of which 54 articles were assessed for quality. The 54 articles assessed covered areas on general health effects (neurobehavioral effects, immunology) and, in particular, genotoxic effects.
In the scientific literature reviewed, there is evidence of exposure to anesthetics, especially nitrous oxide and halogenated gases, being associated with general health and genotoxic risks, but conflicting results have been obtained. The result of this review further stresses the need for scientific knowledge in this area and enhances the studies, above all, on people exposed for long periods.
Full-text · Article · Aug 2008 · Expert Opinion on Drug Safety
[Show abstract][Hide abstract] ABSTRACT: Remifentanil is an ultra-short-acting opioid, increasingly used today in neuroanesthesia and neurointensive care. Its characteristics make remifentanil a potentially ideal agent, but previous data have cast a shadow on this opioid, supporting potentially toxic effects on the ischemic brain. The aim of the present concise review is to survey available up-to-date information on the effects of remifentanil on the central nervous system.
A MEDLINE search within the past seven years for available up-to-date information on remifentanil and brain was performed.
Concise up-to-date information on the effects of remifentanil on the central nervous system was reported, with a particular emphasis on the following topics: cerebral metabolism, electroencephalogram, electrocorticography, motor-evoked potentials, regional cerebral blood flow, cerebral blood flow velocity, arterial hypotension and hypertension, intracranial pressure, cerebral perfusion pressure, cerebral autoregulation, cerebrovascular CO(2) reactivity, cerebrospinal fluid, painful stimulation, analgesia and hyperalgesia, neuroprotection, neurotoxicity and hypothermia.
The knowledge of the influence of remifentanil on brain functions is crucial before routine use in neuroanesthesia to improve anesthesia performance and patient safety as well as outcome.
[Show abstract][Hide abstract] ABSTRACT: Transcranial Doppler (TCD) is widely used to investigate the effects of anesthetic drugs on cerebral blood flow. Its repeatability and non-invasivity makes it an ideal, first choice method. Anesthesia providers are required to be conscious of the cerebral hemodynamic effects of drugs given in their practice, especially in neurosurgery and in subjects with impaired brain functions. The purpose of this review is to present the basic concepts of the TCD technique and the effects on cerebral hemodynamics of the most popular anesthetic drugs evaluated using TCD ultrasonography.
[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · Feb 2006 · The Scientific World Journal