[Postoperative cognitive dysfunction (POCD): strategy of prevention, assessment and management]. / Dysfonctions cognitives postopératoires: stratégie de prévention, de dépistage et de prise en charge.

The femoral neck fracture is a major cause of morbidity and mortality in the elderly. The etiology of cognitive impairment observed in this population of aged patient seems to be multifactorial. In the strategy of prevention, elderly patient must have the clearer information dealing with the postoperative cognitive dysfunction. This would reduce the incidence of POCD and some cognitive complaints, which often reflect the anxiety of the elderly patient facing the possibility of cognitive impairment. During the anaesthesia consultation, it seems important to assess the cognitive function of this elderly patient (like using neuropsycholgical scale as the MMSE) and to identify associated risk factors of cognitive dysfunction. The management of cognitive disorders should be multidisciplinary, the anesthesiologist being the main referent, in collaboration with the geriatrician and the surgeon. In the clinical setting of femoral neck fracture in the elderly, this multimodal management (pain, nutrition, functional rehabilitation to make these patients autonomous as quickly as possible), seems to improve the functional prognosis and to have the observed POCD decreased.

Influence of preoperative cognitive status on propofol requirement to maintain hypnosis in the elderly.

BACKGROUND: The loss of cholinergic neurones in the basal forebrain has been shown to correlate to the extent of cognitive dysfunction during ageing in humans and to the hypnotic potency of propofol in animal models. We examined how the preoperative cognitive status, as assessed by mini-mental state examination (MMSE), may interact with propofol consumption during anaesthesia in the elderly. METHODS: In a prospective study, we recruited 41 patients (65-99 yr) undergoing surgery for hip fracture. Femoral nerve block was performed for analgesia. Target-controlled infusion of propofol (Schnider's model) was adjusted to the bispectral index within the range 40-60. Multiple linear regression analysis determined whether age, BMI, gender, duration of anaesthesia, and preoperative MMSE score affected the propofol consumption (general linear model, Systat 8.0). RESULTS: BMI and MMSE score significantly affected the mean value of propofol consumption. A low MMSE score (below 19) was associated with an observed decrease in propofol requirement in patients >65 yr of age. No significant effect of age, gender, and duration of anaesthesia on the propofol consumption was observed. CONCLUSIONS: Propofol requirement to maintain hypnosis during general anaesthesia appears to decrease with deterioration in the cognitive status in the elderly. We suggest that a cognitive dysfunction linked to a cerebral cholinergic dysfunction may influence the brain sensitivity for propofol in aged patients.

[Biological rhythms for anaesthesia and intensive care]. / L'anesthésie-réanimation et les rythmes biologiques.

Knowledge of biological rhythms has led to better understanding of the time-of-day dependent effects of anaesthetic drugs. These chronopharmacological effects are currently explained by the biological rhythms modulating the pharmacokinetic, toxic and pharmacodynamic parameters of these substances. Such effect has been described for general anesthetics, local anaesthetics, analgesics as well as for antibiotics. But recent data also highlight that general anaesthetics, probably part of their brain effects, also alter the regulation of biological rhythms, including the sleep-wake or the endogenous circadian temperature rhythms. This desynchronization of biological rhythms can led to disturbance of the circadian secretion of many substances, including hormones. Finally, biological rhythms have been also described with regard to physiology of pain and cardiovascular physiopathology. The concept of biological rhythm should be present in mind not only for the clinical management of patients but also for setting studies in the field of anaesthesia, pain and intensive care.

[Postoperative ischemic acute stroke and thrombolytic therapy]. / Thrombolyse postopératoire immédiate dans un contexte d'accident vasculaire sylvien gauche.

Intravenous thrombolytic therapy for ischemic stroke was performed on a 75-year-old patient at recovery from cervicocephalic superficial surgery. The patient recovered totally from ischemic stroke and no neurologic sequelae was observed. Thrombolytic therapy must be performed in an intensive care unit in order to manage some bleeding events which can occur.

Desynchronization of daily rest-activity rhythm in the days following light propofol anesthesia for colonoscopy.

Anesthesia and surgery are associated with fatigue and sleep disorders, suggestive of disturbance of the circadian rest-activity rhythm. Previous studies on circadian rhythm disturbance were focused on patients undergoing general anesthesia associated with surgery. This does not permit one to draw valid conclusions about the effects of general anesthesia per se on circadian rhythms. Our study was set up to determine the impact of a hypnotic dose of propofol on the circadian rest-activity rhythm in humans under real-life conditions. Seventeen healthy subjects scheduled to receive light propofol anesthesia for ambulatory colonoscopy were investigated. Their rest-activity rhythms were assessed using actigraphic monitoring. Diurnal rest was increased, whereas nocturnal sleep was unchanged in the days following anesthesia. Nonparametric analyses showed a decrease in the strength of coupling of the rhythm to stable environmental zeitgebers and increase of fragmentation of the rhythm after anesthesia. Light general anesthesia itself impairs synchronization of the circadian rest-activity rhythm to local time in patients by acting directly on the circadian clock.

[Pathophysiology of post-operative cognitive dysfunction: current hypotheses]. / Physiopathologie de la dysfonction cognitive postopératoire du sujet âgé: hypothèses actuelles.

Post-operative cognitive dysfunction (POCD) has been reported after a variety of surgical procedures. POCD is associated with a decline in performance of activities of daily living of elderly patients and can cause substantial damage to family and/or to social support systems. The incidence of POCD in the first week after surgery is 23% in patients between 60 and 69 years of age and 29% in patients older than 70. Cognitive dysfunction was still present in 14% of patients over 70 at three month after surgery. The risk of POCD increases with age, and the type of surgery is also important since there is very low incidence of POCD after minor surgery. For many years, it has been known that general anaesthesia is associated with persistent changes in gene expression in the brain for at least 72 hours. These observed modifications suggest an interesting hypothesis to explain the side effects of anaesthetic agents on cognitive dysfunction, particularly in the elderly. The inflammatory response to surgery is consistent with the hypothesis that inflammation contributes to cognitive decline in the elderly. Most of the drugs administered during anaesthesia interact with the cerebral cholinergic system, which seems to be impaired with ageing. One can hypothesize that this cholinergic dysfunction is a potent factor in the pathogenesis of POCD. These findings have implications for the information provided before obtaining consent from elderly patients prior to surgery; a careful evaluation of mental status is mandatory for all elderly patients undergoing general anaesthesia. Perioperative physicians should be familiar with the prevention, diagnosis, and management of postoperative cognitive dysfunction.

[Systemic Candida albicans infection with neuromeningeal complication in a premature infant]. / Complication neuroméningée d'une infection systémique à Candida albicans chez un prématuré

INTRODUCTION: Systemic maternal-fetal Candida albicans infections are uncommon diseases with a poor outcome. An associated cerebromeningeal infection increases morbidity. We present a case of neuromeningeal candidiasis following systemic neonatal infection in a premature infant. Management and therapeutic difficulties are outlined. OBSERVATION: The patient was a male infant born preterm at 30 weeks gestation. During his first week of life, he developed a systemic infection with an associated symptomatic hydrocephalus. Systemic candidaisis with neuromeningeal complication was diagnosed five weeks later. Despite treatment including cerebrospinal fluid (CSF) shunting and antimycotic medications (flucytosin and amphotericin B), the candidal infection did not resolve. Infectious and mechanical complications of the CSF drainage were treated by several surgical interventions during the following months. At 10 months of life, there was clinical and laboratory evidence of active persistent neuromeningeal candidaisis. Finally, candidal infection was eradicated with intravenous administration of fluconazole. After five year follow-up, the intellectual and psychological status of the patient was quite satisfactory, and no neurological deficits were found on clinical examination. DISCUSSION: Management of neuromeningeal candidaisis in premature infants is a challenging task particularly because of delayed diagnosis. Candida infection should routinely be suspected in cases of systemic infection with neurological impairment in premature infants. Fluconazole may constitute an efficient therapeutic option.

Mechanisms of action of midazolam on expression of contextual fear in rats.

BACKGROUND: Midazolam may suppress conditioned fear after an aversive event by disrupting the memory trace formed during conditioning, by altering the emotional part of the aversive event, or by the combination of both effects. The purpose of the present study was to determine whether affective-related processes contribute to the amnesic-like effects of midazolam on aversive events. METHODS: The effects of acute administration of low doses of midazolam (0.37-3 mg kg(-1)) on fear conditioning (association between a neutral context and an aversive stimulus) and on innate anxiety in fearful surroundings were examined in rats. The effect of midazolam on the deleterious consequences of pre-exposure to the context (a non-aversive event) for subsequent fear conditioning was then compared with its effect on fear conditioning. The role of midazolam as an affective context was assessed by performing the testing phase under midazolam. Possible locomotor impairment or long-term effects of midazolam were controlled in additional experiments. RESULTS: Midazolam reduced both contextual fear conditioning and spontaneous fear. The deleterious effect of midazolam on pre-exposure to the context was of the same magnitude as its effect on the acquisition phase of fear conditioning. The effects of midazolam on both pre-exposure to the context and fear conditioning were unchanged when rats received a second injection of midazolam before the retention phase. CONCLUSIONS: Low doses of midazolam that do not impair locomotion suppress conditioned fear to the context by acting on memory processes rather than on affective or anxiolytic processes.

VACUTEX: a dressing designed for patients, tailored by nurses.

VACUTEX is a new rapid capillary action dressing comprising three layers: two 100% polyester filament outer layers, and a 65% polyester and 35% cotton woven inner layer. The outer surfaces are fused in such a way as to prevent micro fibres shedding within the wound bed. No two wounds are alike, and wounds are often located in difficult-to-dress areas. This article will describe how VACUTEX, when used with creativity, addresses many of the challenges of wound management.

[How to read a scientific paper. Committee for Clinical References of the French Anesthesia and Resuscitation Society]. / Aide à la lecture d'une étude scientifique. Comité des référentiels cliniques de la Société française d'anesthésie et de réanimation.

Every scientific article has to undergo a critical reading before its conclusions can be accepted. This article discusses the tools for assessing the scientific value of a study. A sequence of methodological criteria allows quality evaluation of an article and its classification in a scale of level of proof.

Combined lesions of cholinergic and serotonergic neurons in the rat brain using 192 IgG-saporin and 5,7-dihydroxytryptamine: neurochemical and behavioural characterization.

This study assessed behavioural and neurochemical effects of i.c.v. injections of both the cholinergic toxin 192 IgG-saporin (2 microgram) and the serotonergic toxin 5,7-dihydroxytryptamine (5,7-DHT; 150 microgram) in Long-Evans female rats. Dependent behavioural variables were locomotor activity, forced T-maze alternation, beam walking, Morris water-maze (working and reference memory) and radial-maze performances. After killing by microwave irradiation, the concentrations of acetylcholine, monoamines and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hippocampus, frontoparietal cortex and striatum. 192 IgG-saporin reduced the concentration of acetylcholine by approximately 40% in the frontoparietal cortex and hippocampus, but had no effect in the striatum. 5,7-DHT lesions reduced the concentration of serotonin by 60% in the frontoparietal cortex and 80% in the hippocampus and striatum. Noradrenaline was unchanged in all structures except the ventral hippocampus where it was slightly increased in rats given 192 IgG-saporin. Cholinergic lesions induced severe motor deficits but had no other effect. Serotonergic lesions produced diurnal and nocturnal hyperactivity but had no other effect. Rats with combined lesions were more active than those with only serotonergic lesions, showed motor dysfunctions similar to those found in rats with cholinergic lesions alone, and exhibited impaired performances in the T-maze alternation test, the water-maze working memory test and the radial-maze. Taken together and although cholinergic lesions were not maximal, these data show that 192 IgG-saporin and 5,7-DHT lesions can be combined to selectively damage cholinergic and serotonergic neurons, and confirm that cholinergic-serotonergic interactions play an important role in some aspects of memory, particularly in spatial working memory.

Central cholinergic depletion induced by 192 IgG-saporin alleviates the sedative effects of propofol in rats.

We examined the effect of central cholinergic depletion on the sedative potency of propofol in rats. Depletion was produced by intracerebroventricular administration of an immunotoxin specific to cholinergic neurones (192 IgG-Saporin; 2 microg). As a result of this lesion, acetylcholine concentration was reduced by about 40% in the frontoparietal cortex and in the hippocampus but was essentially normal in the striatum and cerebellum. Sedation in rats was assessed as the decrease in locomotor activity. Sedative potency of propofol (30 mg kg(-1) i.p.) was reduced by about 50% in rats who received the injection of 192 IgG-Saporin as compared to controls. These results show that a central cholinergic depletion alleviates the sedative effect of propofol, and indicates that basal forebrain cholinergic neurones might mediate part of the sedative/hypnotic effects of propofol.

Effect of nonsedative doses of propofol on an innate anxiogenic situation in rats.

BACKGROUND: The effect of propofol on anxiety has not been well studied. In humans, such investigations are confused by the fact that sedation often coexists with anxiolysis. Therefore, the authors evaluated the effects of minimal sedation with propofol in rats placed in an innate anxiogenic situation, the elevated plus-shaped maze. METHODS: In experiment 1, spontaneous locomotor activity was determined in rats as a measure of sedative effect induced by propofol (0-9 mg/kg administered intraperitoneally). In experiment 2, groups of rats received propofol (0-9 mg/kg) or diazepam (0-2 mg/kg) and then were placed on a plus-shaped maze elevated above the ground that was composed of two opposite closed arms and two opposite open arms. On an initial exposure to the maze, undrugged rats avoid the open arms, with the number of entries into and time spent within the open arms constituting approximately 20% of their total activity. This reflects normal anxiety in a rodent for any elevated open platform. RESULTS: In experiment 1, 0-9 mg/kg propofol did not alter spontaneous activity in rats. In experiment 2, propofol and diazepam significantly increased the number of entries into and the time spent within the open arms. Propofol at a dose of 9 mg/kg significantly increased the rats' level of exploration of the open arms to about 50% of all exploratory activity, and a similar observation was made with 2 mg/kg diazepam. CONCLUSIONS: In a standard animal model, propofol has anxiolytic properties at doses that do not produce sedation.

[The sitting position in neurosurgery: the viewpoint of the surgeon]. / La position assise en neurochirurgie: le point de vue du chirurgien.

The sitting position offers the benefits of better access to the apex of the posterior fossa, and an improved exploration and dissection because blood and cerebral spinal fluid drain away from the operative site. Specific complications of the sitting position include cardiovascular instability, jugular venous obstruction, airway oedema, quadriplegia, displacements of catheters and the endotracheal tube, ulnar, sciatic and lateral peroneal nerve compression, venous air embolism, and tension pneumocephalus. In the only existing comparative study, the differences were an increased bleeding in the horizontal position and a better cranial nerve preservation in the sitting position. This argues strongly for teaching and use of the sitting position whenever surgically indicated.

[Intracranial surgery in the lateral position]. / Abord intracrânien en position latérale.

The lateral posture (Park Bench) is now widely used. It provides a comfortable position for the surgeon and a convenient brain relaxation. However the positioning is complex and carries a risk of stretching of the brachial plexus. Spatial orientation is more difficult and requires surgical experience. The lateral position does not modify the haemodynamic and respiratory function in healthy patients. In the opposite, various cardiac or respiratory effects of right or left lateral position can occur in patients with cardiac and/or respiratory pathology.

The anxiolytic effect of gamma-hydroxybutyrate in the elevated plus maze is reversed by the benzodiazepine receptor antagonist, flumazenil.

The effects of gamma-hydroxybutyrate (GHB), a product of gamma-aminobutyric acid (GABA) metabolism which possesses neuromodulatory properties in brain, were investigated in the elevated plus maze in rats. The number of entries and the time spent in the open arms of the maze were increased by GHB (50, 150, 250 mg/kg i.p.). This is classically considered as indicative of an anxiolytic effect of the drug. There was no sedative effect at these doses as measured by the spontaneous locomotor activity in the actimeter or the total number of arm entries. The anxiolytic properties of GHB were reversed by neither the GHB receptor antagonist, NCS-382 (6,7,8,9-tetrahydro-5(H)-5-olylidene acetic acid) (300 mg/kg i.p.), nor the opioid receptor antagonist, naloxone (10 mg/kg i.p.). However the anti-anxiety effect of GHB was antagonized by the benzodiazepine receptor antagonist, flumazenil (10 mg/kg i.p.), suggesting an interaction of GHB with the GABA(A) receptor complex which mediates the anti-anxiety effect of benzodiazepines.

Effect of midazolam on propofol-induced positive affective state assessed by place conditioning in rats.

BACKGROUND: The effect of either midazolam or the combination of midazolam and propofol on the affective state was assessed in rats at subanesthetic doses and at recovery from anesthesia. METHODS: The putative drug(s)-induced affective states were repeatedly paired with one of two distinguishable compartments of an experimental cage, whereas the vehicle(s)-induced effect was repeatedly paired with the other compartment. During a subsequent choice test for one compartment over the other, the rats' preference for the drug(s)-paired compartment over the vehicle(s)-paired compartment is indicative of a pleasant state induced by the drug(s). In experiment 1, rats were conditioned with different doses of midazolam either at subanesthetic states or at recovery from anesthesia. In experiment 2, groups of rats were conditioned with different combinations of midazolam and propofol either at subanesthetic states or at recovery from anesthesia induced jointly by midazolam (10 mg/kg) and propofol (60 mg/kg). Experiment 3 was conducted in the same way as experiment 2, except that midazolam was paired with both compartments. In addition, these groups were tested not only in an undrugged state but also in a drugged (with midazolam) state. RESULTS: In experiment 1, rats exhibited a place preference for the environment previously associated with midazolam, at subanesthetic and anesthetic doses. Experiment 2 showed that a propofol-induced place preference was found to be dose-dependently suppressed by midazolam. Experiment 3 replicated the findings of experiment 2 and extended them to the mechanism by which midazolam blocked a propofol-induced place preference. CONCLUSIONS: Midazolam administered before propofol blocked the expression of a propofol-induced pleasant state.

Early assessment of transplanted liver function: lignocaine clearance test (MEGX).

The purpose of this study was to assess the value of lignocaine biotransformation into monoethylglycinexylidide (MEGX) and conventional liver function tests in the early post-operative period as an indicator of graft function and as a diagnostic tool for complications after hepatic transplantation. Monoethylglycinexylidide formation, plasma bilirubin, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), factor V index (FVI) and prothrombin time index (PTI) were measured in 71 patients undergoing 80 liver transplantations respectively at 12 (T1), 24 (T2), 48 (T3) and 72 h (T4) after liver graft revascularization. Patients were divided into two group according to the post-operative outcome. Patients with favourable outcome (n = 59) had significantly higher monoethylglycinexylidide synthesis, higher factor V index and prothrombin time index plasma concentrations, lower bilirubin, ASAT and ALAT plasma concentration (P < 0.0001 at T2 and T3) than those with complicated time course (n = 21). Monoethylglycinexylidide synthesis was the best discriminant of a favourable outcome, whereas bilirubin and ALAT concentrations were associated with complications (bilirubin for primary non function [PNF], ALAT for acute rejection). Thus, the combination of parameters at T2 was a very efficient predictor of primary non function, acute rejection and an uncomplicated time course.

Effect of propofol on affective state as assessed by place conditioning paradigm in rats.

BACKGROUND: Whether propofol produces a pleasant affective state remains unclear from clinical studies. In the current study, the effect on affective state of subanesthetic and anesthetic doses of propofol was assessed at a preclinical level with rats in a place conditioning paradigm. Propofol was compared with methohexital. METHODS: In the place conditioning paradigm, propofol-induced effect was repeatedly paired with one of two distinguishable compartments of the apparatus, whereas the vehicle-induced effect was repeatedly paired with the other compartment. During a subsequent free-choice test, a preference for the drug-paired compartment over the vehicle-paired compartment would be indicative of pleasant state induced by the drug. For all experiments, the conditioning session lasted 8 days and consisted of four pairings of the drug with one compartment and four pairings of the equivalent volume of vehicle with the other compartment. In experiment 1A, four groups of rats were designated according to the dose of propofol that they received intraperitoneally: 0,30,60, or 90 mg/kg. In experiment 1B, the same procedure was used with subanesthetic doses of intraperitoneal methohexital: 0,10,20, or 30 mg/kg. In experiment 2, the rats were conditioned during the recovery period from short-term anesthesia. For one group, anesthesia was induced by propofol (100 mg/kg) whereas for the other group, anesthesia was induced by an equivalent anesthetic dose of methohexital (40 mg/kg). RESULTS: In experiment 1A, the 30-mg/kg, 60-mg/kg, and 90-mg/kg groups showed a place preference for the drug-paired compartment, but only the group conditioned with 60 mg/kg propofol significantly differed from the 0-mg/kg group. In experiment 1B, the groups conditioned with methohexital showed no place preference for the drug-paired compartment. In experiment 2, the rats showed a place preference for the compartment in which they recovered from propofol-induced anesthesia but no place preference for the compartment in which they recovered from methohexital-induced anesthesia. CONCLUSIONS: Propofol, but not methohexital, induced a pleasant affective state in rats at subanesthetic doses as well as during recovery from an anesthetic dose.