Recommendations for the Nomenclature of Cognitive Change Associated with Anaesthesia and Surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines (Diagnostic and Statistical Manual for Mental Disorders, fifth edition [DSM-5] and National Institute for Aging and the Alzheimer Association [NIA-AA]) are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions. Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Recommendations for the Nomenclature of Cognitive Change Associated With Anaesthesia and Surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Isoflurane affects the cytoskeleton but not survival, proliferation, or synaptogenic properties of rat astrocytes in vitro.

BACKGROUND: More than half of the cells in the brain are glia and yet the impact of general anaesthetics on these cells is largely unexamined. We hypothesized that astroglia, which are strongly implicated in neuronal well-being and synapse formation and function, are vulnerable to adverse effects of isoflurane. METHODS: Cultured rat astrocytes were treated with 1.4% isoflurane in air or air alone for 4 h. Viability, proliferation, and cytoskeleton were assessed by colorimetric assay, immunocytochemistry, or a migration assay at the end of treatment or 2 days later. Also, primary rat cortical neurones were treated for 4 days with conditioned medium from control [astrocyte-conditioned media (ACM)], or isoflurane-exposed astrocytes (Iso-ACM) and synaptic puncta were assessed by synapsin 1 and PSD-95 immunostaining. RESULTS: By several measures, isoflurane did not kill astrocytes. Nor, based on incorporation of a thymidine analogue, did it inhibit proliferation. Isoflurane had no effect on F-actin but reduced expression of α-tubulin and glial fibrillary acidic protein both during exposure (P<0.05 and P<0.001, respectively) and 2 days later (P<0.01), but did not impair astrocyte motility. ACM increased formation of PSD-95 but not synapsin 1 positive puncta in neuronal cultures, and Iso-ACM was equally effective. CONCLUSIONS: Isoflurane decreased expression of microtubule and intermediate filament proteins in astrocytes in vitro, but did not affect their viability, proliferation, motility, and ability to support synapses.

Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar.

Although previously considered entirely reversible, general anaesthesia is now being viewed as a potentially significant risk to cognitive performance at both extremes of age. A large body of preclinical as well as some retrospective clinical evidence suggest that exposure to general anaesthesia could be detrimental to cognitive development in young subjects, and might also contribute to accelerated cognitive decline in the elderly. A group of experts in anaesthetic neuropharmacology and neurotoxicity convened in Salzburg, Austria for the BJA Salzburg Seminar on Anaesthetic Neurotoxicity and Neuroplasticity. This focused workshop was sponsored by the British Journal of Anaesthesia to review and critically assess currently available evidence from animal and human studies, and to consider the direction of future research. It was concluded that mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes. However, definitive clinical data remain elusive. Since general anaesthesia often cannot be avoided regardless of patient age, it is important to understand the complex mechanisms and effects involved in anaesthesia-induced neurotoxicity, and to develop strategies for avoiding or limiting potential brain injury through evidence-based approaches.

Measurement of post-operative cognitive dysfunction after cardiac surgery: a systematic review.

Post-operative cognitive dysfunction (POCD) is a decline in cognitive function from pre-operative levels, which has been frequently described after cardiac surgery. The purpose of this study was to examine the variability in the measurement and definitions for POCD using the framework of a 1995 Consensus Statement on measurement of POCD. Electronic medical literature databases were searched for the intersection of the search terms 'thoracic surgery' and 'cognition, dementia, and neuropsychological test.' Abstracts were reviewed independently by two reviewers. English articles with >50 participants published since 1995 that performed pre-operative and post-operative psychometric testing in patients undergoing cardiac surgery were reviewed. Data relevant to the measurement and definition of POCD were abstracted and compared with the recommendations of the Consensus Statement. Sixty-two studies of POCD in patients undergoing cardiac surgery were identified. Of these studies, the recommended neuropsychological tests were carried out in less than half of the studies. The cognitive domains measured most frequently were attention (n=56; 93%) and memory (n=57; 95%); motor skills were measured less frequently (n=36; 60%). Additionally, less than half of the studies examined anxiety and depression, performed neurological exam, or accounted for learning. Four definitions of POCD emerged: per cent decline (n=15), standard deviation decline (n=14), factor analysis (n=13), and analysis of performance on individual tests (n=12). There is marked variability in the measurement and definition of POCD. This heterogeneity may impede progress by reducing the ability to compare studies on the causes and treatment of POCD.

Nonnutritive sweeteners: taste-structure relationships for some new simple dihydrochalcones.

Six sweet and five nonsweet simple nonglycosidic dihydrochalcones were prepared, two of which have properties comparable to those of the intensely sweet neohesperidin dihydrochalcone.

Inversion of excited States of transition-metal complexes.

The nature of the emission from central metal ions in complexes can be controlled by chemical alteration of the ligands. For iridium(III) species three types of emission have been observed, each originating from a different and orbitally identifiable excited state. Principles useful for designing new luminescent materials are formulated. They can be used for guiding photochemical research and for designing new analytical methods.

Delirium is associated with early postoperative cognitive dysfunction.

The purpose of this analysis was to determine if postoperative delirium was associated with early postoperative cognitive dysfunction (at 7 days) and long-term postoperative cognitive dysfunction (at 3 months). The International Study of Postoperative Cognitive Dysfunction recruited 1218 subjects >or= 60 years old undergoing elective, non-cardiac surgery. Postoperatively, subjects were evaluated for delirium using the criteria of the Diagnostic and Statistical Manual. Subjects underwent neuropsychological testing pre-operatively and postoperatively at 7 days (n = 1018) and 3 months (n = 946). Postoperative cognitive dysfunction was defined as a composite Z-score > 2 across tests or at least two individual test Z-scores > 2. Subjects with delirium were significantly less likely to participate in postoperative testing. Delirium was associated with an increased incidence of early postoperative cognitive dysfunction (adjusted risk ratio 1.6, 95% CI 1.1-2.1), but not long-term postoperative cognitive dysfunction (adjusted risk ratio 1.3, 95% CI 0.6-2.4). Delirium was associated with early postoperative cognitive dysfunction, but the relationship of delirium to long-term postoperative cognitive dysfunction remains unclear.

Recommendations for the Nomenclature of Cognitive Change Associated with Anaesthesia and Surgery-20181.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Gene expression following acute morphine administration.

The long-term response to neurotropic drugs depends on drug-induced neuroplasticity and underlying changes in gene expression. However, alterations in neuronal gene expression can be observed even following single injection. To investigate the extent of these changes, gene expression in the medial striatum and lumbar part of the spinal cord was monitored by cDNA microarray following single injection of morphine. Using robust and resistant linear regression (MM-estimator) with simultaneous prediction confidence intervals, we detected differentially expressed genes. By combining the results with cluster analysis, we have found that a single morphine injection alters expression of two major groups of genes, for proteins involved in mitochondrial respiration and for cytoskeleton-related proteins. RNAs for these proteins were mostly downregulated both in the medial striatum and in lumbar part of the spinal cord. These transitory changes were prevented by coadministration of the opioid antagonist naloxone. Data indicate that microarray analysis by itself is useful in describing the effect of well-known substances on the nervous system and provides sufficient information to propose a potentially novel pathway mediating its activity.

Dihydrochalcone sweeteners. A study of the atypical temporal phenomena.

Neohesperidin dihydrochalcone (NHDHC), known since 1963 as an intensely sweet compound, is determined to be 340 +/- 60 (p less than 0.05) times more potent than sucrose. The unusual temporal properties of this material are hypothesized as being due to the effects of metabolism, conformation, chelation, or hydrophobicity. Forty-four analogues are synthesized to test the four hypotheses, none of which are strongly supported. A method of quantitation of temporal characteristics of tastant molecules is developed so as to allow comparison of taste appearance time (AT) and extinction time (ET) of experimental compounds. Four of the new compounds, 40 and 43-45, exhibit high sweetness potencies, ranging from 280 and 440 times sucrose, and may be useful in selected food systems. The temporal taste characteristics remain unimproved over NHDHC, however.

Intact nociception-induced neuroplasticity in transgenic mice deficient in neuronal nitric oxide synthase.

Nitric oxide is thought to play an important role in multiple forms of use-dependent synaptic plasticity, including that which follows noxious peripheral stimulation. This suggests that development of nociception-induced neuroplasticity should be impaired in transgenic animals lacking the neuronal form of nitric oxide synthase. We used the formalin model of nociception to test this hypothesis in wild-type and nitric oxide synthase knockout mice. Formalin-induced nociceptive behavior was intact in the knockout mice. Furthermore, administration of a nitric oxide synthase inhibitor blocked nociception-induced neuroplasticity in wild-type mice but had no effect in the knockouts, whereas inhalation of the gaseous analgesic nitrous oxide attenuated development of neuroplastic changes in both phenotypes. These data indicate that nitric oxide is sufficient but not essential for development of nociception-induced neuroplasticity.

Ventricular performance and glucose uptake in rats during chronic hypobaric hypoxia.

To identify changes of ventricular performance and their relationship to myocardial glucose uptake in Sprague-Dawley rats exposed to hypobaric hypoxia, radionuclide angiocardiograms (n = 34) and 2-[14C]deoxyglucose (2-[14C]DG) autoradiography (n = 14) were performed on rats maintained either for two weeks in air at 380 mmHg (hypoxic group), two weeks in hypobaric hypoxia followed by two weeks of air (recovered group), or in air (control group). Right ventricular ejection fraction (RVEF) was 66% +/- 2% (mean +/- s.e.m.) in controls, 40% +/- 3% during hypoxia, and 60% +/- 2% in recovered rats. LVEF remained unchanged. In controls, RV 2-[14C]DG uptake was 77% +/- 3% of LV uptake. During hypoxia, 2-[14C]DG uptake increased. This increase was greater within the RV than the LV and septum (85 +/- 16% versus 51 +/- 10%, p less than 0.005). The alterations of RV 2-[14C]DG uptake correlated with systolic pulmonary artery pressure (r = 0.77, p = 0.002).

Naloxone pretreatment alters the local cerebral metabolic effect of gamma-hydroxybutyrate in rats.

The effect of naloxone on gamma-hydroxybutyrate (GHB)-induced cerebral metabolic depression was studied in rats with the 2-[14C]deoxyglucose method. Naloxone pretreatment statistically significantly antagonized the cerebral metabolic effect of GHB in 10 of 38 structures examined. These results are consistent with previous data showing reversal of the dopaminergic, electroencephalographic, and behavioral effects of GHB by naloxone and suggest that some of the neuropharmacological effects of GHB are mediated by the endogenous opiate system.

Effect of SCH 39166, a novel dopamine D1 receptor antagonist, on [3H]acetylcholine release in rat striatal slices.

SCH 39166 is a novel and selective dopamine D1 receptor antagonist. It has been reported to have potential antipsychotic properties and reduced extrapyramidal side-effect liabilities (EPS). The current studies investigated the pharmacological effects of SCH 39166 on striatal cholinergic function in order to further characterize its dopamine D1 receptor selectivity and to address its EPS liability. Electrically stimulated [3H]acetylcholine (ACh) release from rat striatal slices was measured and comparisons were made between SCH 39166, SCH 23390, (-)-sulpiride, haloperidol or apomorphine on their effect on [3H]ACh release. Results indicated that apomorphine inhibited [3H]ACh release from striatal slices (IC50 = 0.31 microM). (-)-Sulpiride and haloperidol completely reversed the inhibition of [3H]ACh release seen with apomorphine. In contrast, SCH 39166, as well as, SCH 23390 did not reverse the inhibition of [3H]ACh release induced by apomorphine. These findings indicate that dopamine D2 receptors are primarily involved in modulation of [3H]ACh release. Furthermore, selective dopamine D1 receptor antagonists, such as SCH 39166, are ineffective in modulating striatal [3H]ACh release, suggesting that striatal cholinergic hyperactivity and possibly EPS will not be a consequence of dopamine D1 receptor blockade.

SCH 57790, a selective muscarinic M(2) receptor antagonist, releases acetylcholine and produces cognitive enhancement in laboratory animals.

The present studies were designed to assess whether the novel muscarinic M(2) receptor antagonist 4-cyclohexyl-alpha-[4[[4-methoxyphenyl]sulphinyl]-phenyl]-1-piperazineacetonitrile (SCH 57790) could increase acetylcholine release in the central nervous system (CNS) and enhance cognitive performance in rodents and nonhuman primates. In vivo microdialysis studies show that SCH 57790 (0.1-10 mg/kg, p.o.) produced dose-related increases in acetylcholine release from rat hippocampus, cortex, and striatum. SCH 57790 (0.003-1.0 mg/kg) increased retention times in young rat passive avoidance responding when given either before or after training. Also, SCH 57790 reversed scopolamine-induced deficits in mice in a passive avoidance task. In a working memory operant task in squirrel monkeys, administration of SCH 57790 (0.01-0.03 mg/kg) improved performance under a schedule of fixed-ratio discrimination with titrating delay. The effects observed with SCH 57790 in behavioral studies were qualitatively similar to the effects produced by the clinically used cholinesterase inhibitor donepezil, suggesting that blockade of muscarinic M(2) receptors is a viable approach to enhancing cognitive performance.

Local cerebral glucose utilization in the homozygous Brattleboro rat.

The [14C]deoxyglucose technique was used to measure brain glucose utilization in homozygous male Brattleboro and age-matched Long-Evans control rats. Brattleboro homozygotes had significantly higher daily water intakes and plasma osmolalities and significantly lower body weights than controls. Glucose utilization for the brain as a whole and for 46 discrete brain structures was not significantly different for the two strains. Our results indicate that vasopressin is not essential for the maintenance of overall brain glucose utilization in resting, awake rats.

Correlates of sexual risk-taking among gay male substance abusers.

This paper examines sexual risk-taking within a sample of sexually active gay and bisexual men entering substance abuse treatment (n = 383), and identifies correlates of unprotected anal sex within this group. Sexual risk-taking was high, with 55% of these men engaging in anal intercourse without a condom within a 90-day period. Correlates of unprotected anal sex varied somewhat when looking at unprotected anal sex with a primary partner only and with non-primary partners; substance use variables (number of drugs used, use of inhalant nitrites or stimulant drugs with sex, length of time since use of alcohol/drugs, loss of control problems associated with alcohol/drug use) appear to play more of a role in unprotected anal sex with non-primary partners. Overall, logistic regression analyses indicated that sexual risk was greater for those who were more sexually active, enjoyed unprotected anal sex with withdrawal prior to ejaculation, did not approve of sex outside of a love relationship, and identified themselves as more risky. In addition, those who reported more social problems due to substance use had fewer expectations that substance use increased risk, had been HIV-tested, and used reappraisal/problem-solving coping strategies showed greater risk with a primary partner only. Sexual risk with non-primary partners was greater for those who used more drugs, reported more difficulty avoiding high-risk sex when aroused and were HIV+. The paper discusses the implications of these findings for the design of sexual risk-reduction interventions.