Anaesthetics and postoperative cognitive dysfunction: a pathological mechanism mimicking Alzheimer's disease.

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.

Genotoxic effects of anesthetic agents.

BACKGROUND: Preliminary research results indicate that exposure to anesthetics affects health. OBJECTIVE: To provide, with evidence-based knowledge, the answer to the question: What are the genotoxic effects threatening people exposed to anesthetics? METHOD: 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. RESULTS/CONCLUSION: 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.

Remifentanil and the brain.

BACKGROUND AND AIM: 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. METHOD: A MEDLINE search within the past seven years for available up-to-date information on remifentanil and brain was performed. RESULTS: 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. CONCLUSION: 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.

Transcranial Doppler and anesthetics.

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.

Viagra, surgery and anesthesia: a dangerous cocktail with a risk of blindness.

Since the launch in 1998 of the anti-impotence drug sildenafil (viagra), the American food and drug administration has identified 50 cases of drug-related blindness, the so-called nonarteritic anterior ischemic optic neuropathy. This, very serious, side effect frequently leads to sudden, mostly irreversible loss of vision, and there is no proven effective treatment to cure patients or to prevent recurrence. The mechanism of ischemic optic neuropathy is not clear, but it could be related to the fact that the ophthalmic and central retinal arteries have an autoregulation of their own blood flow without any autonomic nerve supply; vasoreactivity could be lower albeit efficient, and therefore more vulnerable to systemic modifications of the circulation. But decreased visual acuity and loss of visual ability also are, although uncommon, anesthesiological and surgical complications. These data are consistent with the hypothesis that sildenafil, surgery and anesthesia, taken together, could be a potentially dangerous cocktail of risk factors for sudden irreversible loss of vision. To reduce the risk, sildenafil use should be avoided at least one week before surgical operations, since the reported cases of blindness developed 36h after drug ingestion.

Alzheimer's disease and anaesthesia: implications for the central cholinergic system.

Alzheimer's disease (AD) is associated with a loss of cholinergic neurons resulting in profound memory disturbances and irreversible impairment of cognitive function. The central cholinergic system is involved in the action of general anaesthetic agents. Anaesthetic modulation of cholinergic transmission has profound effects on brain function via a cascade of synaptic and postsynaptic events by binding both nicotinic and muscarinic receptors. During general anaesthesia, decrease in acetylcholine release and depression of cholinergic transmission facilitates the desirable effects of general anaesthetics, such as loss of consciousness, pain, voluntary movements and memory. From this point of view, patients with AD, characterized by a compromised neuronal transmission, represent particular cases in which the choice of anaesthesia drugs may have a negative effect on the postoperative outcome. A future challenge may be the identification of brain targets of general anaesthetics which do not expose patients to postoperative cognitive dysfunction, nor interfere with prognosis of brain degenerative disease.

The effect of peribulbar block with ropivacaine on bi-hemispheric cerebral oxygen saturation in aged patients.

We evaluated the effects of peribulbar block for eye surgery on bi-hemispheric regional cerebral oxygenation (rSO2)) of aged patients. In 66 adult patients, peribulbar block was performed using ropivacaine 10 mg.ml(-1) with hyaluronidase 100 IU.ml(-1). Cerebral oxygenation was monitored using continuous non-invasive, near-infrared spectroscopy. The rSO2 data on the side where the eye block was performed were evaluated as eye block side values, whereas the data recorded on the other side were taken as control values. Mean rSO2 values on the side where regional block was performed were not significantly different from control values (p > 0.05). Nevertheless, in several patients, a slight desaturation in the cerebral hemisphere on the block side was detected. Therefore, in aged patients, peribulbar block with ropivacaine does not significantly modify bi-hemispheric rSO2, but rSO2 monitoring during peribulbar block should be a field of future research in aged patients with brain injury or disease.

Cerebral haemodynamic changes during propofol-remifentanil or sevoflurane anaesthesia: transcranial Doppler study under bispectral index monitoring.

BACKGROUND: Sevoflurane or propofol-remifentanil-based anaesthetic regimens represent modern techniques for neurosurgical anaesthesia. Nevertheless, there are potential differences related to their activity on the cerebrovascular system. The magnitude of such difference is not completely known. METHODS: In total 40 patients, treated for spinal or maxillo-facial disorders, were randomly allocated to either i.v. propofol-remifentanil or inhalational sevoflurane anaesthesia. Transcranial Doppler was used to assess changes in cerebral blood flow velocity, carbon dioxide reactivity, cerebral autoregulation and the bispectral index to assess the depth of anaesthesia. RESULTS: Time-averaged mean flow velocity (MFV) was significantly reduced after induction of anaesthesia in both sevoflurane and propofol-remifentanil groups (P<0.001). At deeper levels of anaesthesia, MFV increased in the sevoflurane group, suggesting an uncoupling flow/metabolism, whereas it was further reduced in the propofol-remifentanil group (P<0.001). Indices of cerebral autoregulation were reduced in patients with high-dose sevoflurane whereas autoregulation was preserved in patients anaesthetized with propofol-remifentanil (P<0.001). Higher CO(2) concentrations impaired cerebral autoregulation in the sevoflurane group but not in patients anaesthetized with propofol-remifentanil. CONCLUSIONS: Propofol-remifentanil anaesthesia induced a dose-dependent low-flow state with preserved cerebral autoregulation, whereas sevoflurane at high doses provided a certain degree of luxury perfusion.

Effect of tramadol on Bispectral Index during intravenous anaesthesia with propofol and remifentanil.

The aim of this study was to investigate the effects of tramadol on the Bispectral Index (BIS) during total intravenous propofol-remifentanil anaesthesia. Forty-four adult ASA Physical status I-II patients, scheduled for elective general surgical procedures were included in a prospective observational randomized study. Doses for anaesthetics and opioids were adjusted to keep the BIS value at 50 +/- 5. After 20 minutes of stable anaesthesia, the subjects were randomly allocated to receive intravenous saline (control group) or tramadol 1.5 mg/kg (tramadol group). BIS values, mean arterial pressure, and heart rate were recorded every five minutes for 20 minutes. Mean BIS values after tramadol administration were not significantly different from those following saline, throughout the observation period (P > 0.05). There were no patients in whom BIS values were more than 60 or who presented explicit recall of events under anaesthesia. There were no significant changes in mean arterial pressure, SpO2, or heart rate (P > 0.05). The results indicate that the administration of tramadol during stable total intravenous anaesthesia with propofol-remifentanil does not affect BIS values. The clinical relevance is that tramadol can be safely administered pre- and intraoperatively as pre-emptive or preventive analgesia without modification of the depth of anaesthesia.

Fatal exacerbation of peripheral neuropathy during lamivudine therapy: evidence for iatrogenic mitochondrial damage.

A 57-year-old man with mild neuropathy who was positive for hepatitis B and C viruses was treated with lamivudine 300 mg.day(-1). After 3 months he presented with dysphonia and progressive muscle weakness. Subsequently, he developed tetraparesis followed by acute respiratory failure requiring mechanical ventilation, which was complicated by sudden cardiac arrest. After lamivudine was stopped, the neuropathy improved and respiratory capacity improved. Unfortunately, the patient died suddenly in spite of haemodynamic, ventilatory and metabolic support. Electrophysiological studies showed evidence of a sensory-motor axonal neuropathy. Nerve biopsy, muscle biopsy, biochemistry and mitochondrial DNA molecular genetics suggested possible widespread iatrogenic mitochondrial damage. Mitochondrial DNA dysfunction could be a potential cause of the sudden cardiac arrest. Stopping lamivudine treatment sooner after the onset of peripheral neuropathy or its exacerbation is important as continued therapy could lead to acute respiratory failure requiring mechanical ventilation and intensive care unit admission.

Drugs of anesthesia acting on central cholinergic system may cause post-operative cognitive dysfunction and delirium.

Given the progressive and constant increase of average life expectancy, an increasing number of elderly patients undergo surgery. After surgery, elderly patients often exhibit a transient reversible state of cerebral cognitive alterations. Among these cognitive dysfunctions, a state of delirium may develop. Delirium is an aetiologically non-specific syndrome characterised by concurrent disturbances of consciousness and attention, perception, thinking, memory, psychomotor behaviour and the sleep-wake cycle. Delirium appears to occur in 10-26% of general medical patients over 65, and is frequently associated with a significant increase in morbidity and mortality. During hospitalization, mortality rates have been estimated to be 10-26% of patients who developed post-operative delirium, and 22-76% during the following months. Over the last few decades, post-operative delirium has been associated with several pre-operative predictor factors, as well as age (50 years and older), alcohol abuse, poor cognitive and functional status, electrolyses or glucose abnormalities, and type of surgery. The uncertain pathogenesis of post-operative cognitive dysfunctions and delirium has not permitted a causal approach to developing an effective treatment. General anesthesia affects brain function at all levels, including neuronal membranes, receptors, ion channels, neurotransmitters, cerebral blood flow and metabolism. The functional equivalents of these impairments involve mood, memory, and motor function behavioural changes. These dysfunctions are much more evident in the occurrence of stress-regulating transmission and in the alteration of intra-cellular signal transduction systems. In addition, more essential cellular processes, that play an important role in neurotransmitter synthesis and release, such as intra-neuronal signal transduction and second messenger system, may be altered. Keeping in mind the functions of the central muscarinic cholinergic system and its multiple interactions with drugs of anesthesia, it seems possible to hypothesize that the inhibition of muscarinic cholinergic receptors could have a pivotal role in the pathogenesis not only of post-operative delirium but also the more complex phenomena of post-operative cognitive dysfunction.

Tramadol does not modify the Bispectral Index during anaesthesia with sevoflurane and remifentanil.

BACKGROUND: The aim of this study was to investigate the effects of tramadol administered with ketorolac on the Bispectral Index (BIS) during anaesthesia with sevoflurane and remifentanil. METHODS: Forty-six adult patients, ASA I-III, scheduled for elective minor surgical procedures were studied. Patients were premedicated with remifentanil infusion 0.4 microg kg(-1) min(-1) and anaesthesia was induced 4-5 min later with propofol 1.5 mg kg(-1) and maintained with air-oxygen (FI(O(2)) 0.4), remifentanil 0.1-0.15 microg kg(-1) min(-1) and sevoflurane, adjusted to keep the BIS between 40 and 50. After 20 min of stable anaesthesia, the subjects were allocated randomly to receive i.v. tramadol 1.5 mg kg(-1) and i.v. ketorolac 0.3 mg kg(-1) (tramadol group) or saline (control group). BIS values, mean arterial pressure, heart rate and end-tidal carbon dioxide were recorded every 5 min for 20 min. RESULTS: Mean BIS values after tramadol administration were not significantly different from those recorded in patients receiving saline throughout the period of observation. There were no patients who presented explicit recall of events under anaesthesia. No significant changes in mean arterial pressure, heart rate and end-tidal carbon dioxide were noted after tramadol injection. CONCLUSION: Tramadol, given with ketorolac to prevent postoperative pain, during anaesthesia maintained with sevoflurane and remifentanil at BIS between 40 and 50, does not modify the BIS value.

[Ileum-colon junction benign obstructions]. / Le occlusioni benigne della giunzione ileo-colica.

The Authors discuss on anatomical and functional characteristics of ileum-colon junction, physiological narrowing in alimentary tract and often involved in benign obstruction. They report their series and analyze all inflammatory or not inflammatory diseases potentially involved, by describing them shortly and giving some information about their clinical features and imaging. The treatment of this obstruction will be done as soon as possible, before wall lesions force to make a larger resection.

Acute motor axonal polyneuropathy after a cisatracurium infusion and concomitant corticosteroid therapy.

A 40-yr-old male was admitted to the intensive care unit following blunt chest trauma. He had multiple rib fractures, bilateral pneumothoraces, and acute respiratory failure requiring mechanical ventilation. Sedation was achieved with midazolam and morphine, and later with propofol. The patient was paralysed with a continuous infusion of cisatracurium 1.42-5.75 micro g kg(-1) min(-1). Methylprednisolone 125 mg i.v. every 12 h was also started. After discontinuation of the cisatracurium infusion 7 days later, the patient manifested a flaccid quadriplegia with absence of deep-tendon reflexes. No sensory deficits were observed. Electromyography (EMG), repetitive nerve stimulation testing, and single fibre EMG (SFEMG) were performed at regular intervals after stopping cisatracurium. Clinical symptoms and electrophysiological examinations supported the diagnosis of acute motor axonal polyneuropathy related to concomitant administration of cisatracurium and corticosteroid therapy.

[Treatment of substernal goiter. Our experience]. / Il trattamento del gozzo immerso. La nostra esperienza.

The Authors, after having reviewed substernal goitre natural history, report their five-year experience with this disease, underlining clinical features, therapeutic management, positive results. They examine the several proposed classifications and stress haemodynamic and respiratory complications. At last they shortly discuss about diagnostics and, mainly, about correct therapeutic approach which has two aims to resolve the symptomatology and to prevent relapses.