The recruitment of leukocytes to the sites of inflammation and leukocyte-derived inflammatory mediators contributes to the development of tissue injury associated with inflammatory diseases. The first step in the pathogenesis of inflammatory conditions is adhesion of circulating leukocytes to activated vascular endothelial cell in the inflamed tissues and subsequent transmigration through the endothelial cells. During these processes, leukocytes are activated to secrete a variety of substances such as growth factors, chemokines and cytokines, complement components, proteases, nitric oxide, and reactive oxygen metabolites, which are considered to be one of the primary sources of the tissue injury. Prevention or reduction of leukocyte-endothelial cell adhesion often results in a profound attenuation of the microvasculature and parenchymal cell dysfunction in various animal models of human inflammatory diseases. It has been shown that all aspirin-like non-steroidal anti-inflammatory agents share at least one characteristic in that all of these agents diminish the adhesive interactions required for the accumulation of leukocytes at the site of inflamed tissue. The challenge for future investigations will need to be carefully examined: the relations between leukocyte and endothelial cell interactions, the mechanisms of activation of leukocytes and endothelial cells, and the components of the signaling pathways. Information related to these topics will allow a better understanding of the role of leukocytes in inflammatory tissue injury and the development of novel therapeutic strategies.

Information about physician anaesthesiologist manpower in the countries of the European Union was collected from questionnaires sent to the delegates representing their respective countries on the European Board of Anaesthesiology.

In the countries of the European Union and Switzerland and Norway 40 259 specialist anaesthesiologists are recorded. The number of anaesthesiologists in relation to population varies between as little as 4.4 and 4.6 (Ireland and UK) and as many as 15.6 (Italy), with a mean of 10.8/100 000 inhabitants. There are 11 610 physicians recorded in training in anaesthesiology.

The ratio of trainees to specialists in the European Union countries was 28.8/100, varying from as low as 6.5 in France, to as high as 96.7 and 98/100 in Ireland and the UK respectively.

These figures indicate a wide difference in the numbers of specialists and trainees between the European countries studied. However, the overall mean figure is close to that reported in the USA (9.2/100 000).

Atracurium causes a decrease in systemic vascular resistance (SVR) and mean arterial blood pressure (MAP) which has been ascribed to histamine release. However, histamine receptor blockade does not prevent these decreases completely. The hypotensive side effects of atracurium may not only be caused by histamine. In this study we examined the vasoactive effects of atracurium with and without histamine receptor blockade in an isolated femoral artery preparation of the rabbit. We also investigated whether vasodilatation caused by atracurium depends on the presence of endothelial cells. Tyrode perfused, rabbit femoral arteries were constricted with noradrenaline (NA) to ±70% of their passive diameter. Endothelial function was checked with acetylcholine (ACh). The vessels were divided into two groups. In both groups the responses to histamine (1.0−10−6m) and atracurium (3.2−10−5m) were determined. In group one (n = 5), the histamine and atracurium responses were repeated during histamine receptor blockade. In group two (n = 5), the diameter responses to histamine and atracurium before and after endothelium removal were compared. Also, some vessel segments (n = 5) were histologically prepared and examined for mast cells. The vasodilatory responses to atracurium both with and without histamine receptor blockade were the same. Removal of endothelium caused an increase in the histamine response, while the dilating response to atracurium remained constant. We conclude that in the isolated femoral artery of the rabbit, atracurium induces vasodilatation that is not mediated by histamine release and cannot be prevented with histamine receptor blockade. The mechanism of atracurium induced dilation is independent of the endothelium and is located in the smooth muscle cell.

Twenty-two patients were studied while receiving epidural analgesia with diamorphine after major lower abdominal surgery under combined regional and general anaesthesia. Epidural PCA began when the intra-operative epidural block with bupivacaine wore off enough for the patient to request treatment. It was started with 2 mg of diamorphine and continued with a reducible background infusion that was initially set at 0.2 mg h−1 and supplemented by on-demand doses of 0.2 mg, with a lockout time of 15 min. The patients received routine post-operative monitoring and care, with pain at rest being assessed on a four-point verbal rating scale (VRS, none, mild, moderate, severe) at 5, 10, 15, 30, 45, 60, 90 and 120 min from the start of ePCA, then hourly until 24 h and then 2-hourly until 48 h. VRS on coughing and a 10 cm visual analogue score (VAS) at rest and on coughing were recorded at the same times at 4 h, then 4 hourly until 24 h and then at 48 h, at which times, blood samples were also taken to measure morphine concentrations by radioimmunoassay. Analgesia started promptly and reached a maximum at between 30 and 45 min, accompanied by maximum sedation. Thereafter clinically acceptable analgesia was maintained without undue sedation for 48 h, though pain on coughing was less well controlled than pain at rest. After the initial loading dose of diamorphine, the 95%confidence intervals (CI) for further consumption were 3.7 to 17 mg (average 9.7) in the first 24 h and 2.1 to 12.9 mg (average 6.7 mg) in the second 24 h. The plasma morphine concentrations rose to a plateau by about 15 min, with concentrations within 95% CI from 0 to 11 ng mL−1 (average 5 ng mL−1). The VRS and VAS pain scores were analysed by a conservative approach that treated them as ordinal data, and by a parametric approach that treated them as interval data. Both approaches conveyed broadly similar information about the post-operative analgesia.

This study was designed to investigate whether the advantages of low- and minimal-flow anaesthesia can be combined with the laryngeal mask airway (LMA). Seventy female patients undergoing routine gynaecological surgery were investigated. After induction of anaesthesia and after positioning a laryngeal mask airway nos 3 and 4, patients were ventilated for 20 min with a fresh gas flow of 6L min−1. Thereafter, the flow was reduced to 1L min−1 in 50 patients and to 0.5L min−1 in 20 patients. Once in the proper position,the LMA allowed flow reduction in all patients, indicating that no gas leakage occurred. It is concluded,that the application of low-flow and even minimal-flow anaesthesia is an alternative to high-flow anaesthesia. It can result in high annual savings and minimization of pollution. However, its use should be restricted to those anaesthesiologists who are experienced with the laryngeal mask airway and minimal-flow anaesthesia.

Twenty-three patients undergoing elective coronary artery bypass graft surgery with moderate hypothermic bypass, under opiate-benzodiazepine anaesthesia were investigated during the first 7 h following surgery. Patients with recent myocardial infarct (< 6 weeks), reduced left ventricular ejection fraction (< 40%) or requiring inotropic support were excluded. During the first 3 h after surgery, higher oxygen uptake and oxygen extraction ratio were found in shivering patients (n = 5) compared with non-shivering patients (n = 16). A significant relation was found between oxygen uptake and the oxygen extraction ratio for the pooled data (R = 0.80 and 0.87, in shivering and non-shivering patients, respectively) as well as for the individual patients. A weaker relation was observed between cardiac output and oxygen uptake. The lack of adequate circulatory compensation could be related to the depressant effects of residual anaesthesia on the myocardium, surgical trauma, cardioplegic arrest and to peripheral vasoconstriction.

The mechanisms which lead to secondary brain damage following transient ischaemia are incompletely defined. As discussed in this hypothesis article, the events which lead to such damage could encompass (a) a perturbed membrane handling of calcium, leading to a slow, gradual increase in the free cytosolic calcium concentration (Ca2+i), with subsequent calcium overload of mitochondria, (b) a sustained reduction of protein synthesis which, in the long run, deprives cells of enzymes or trophic factors essential to their survival, or (c) the initiation of an inherent program for cell death.

Results obtained in ischaemia of brief to intermediate duration demonstrate that the ultimate cell death is heralded by a reduction in the respiratory capacity of isolated mitochondria. However, the results fail to demonstrate whether or not such a reduction precedes deterioration of the bioenergetic state which then precipitates cell death. Cyclosporin A (CsA) has recently been shown to dramatically improve the delayed CA1 damage following transient forebrain ischaemia. Since CsA is known to block a deleterious permeability transition (PT) in mitochondria from several tissues in response to calcium accumulation and oxidative stress, the results on CsA effects in forebrain ischaemia support a mitochondrial origin for the delayed cell death. Furthermore, comparisons with the effects of CsA and α-phenyl-N-tert-butyl nitrone (PBN) in thymocytes and other cells undergoing programmed cell death suggest that delayed neuronal damage occurs by a sequence of events akin to those leading to apoptotic cell death. However, whether cell death is apoptotic or necrotic may depend on the severity of the insult (and its duration). We speculate that the initial ischaemic transient leads to gradual mitochondrial calcium overload, the latter triggering a PT, and apoptotic or necrotic cell death.

Since similar results have been obtained in normoglycaemic animals subjected to ischaemia of intermediate duration, and in animals with preischaemic hyperglycaemia, it seems likely that both increased ischaemia duration and hyperglycaemia accelerate damage to mitochondria in the reperfusion period.

Recent results obtained in transient focal ischaemia of 2 h duration demonstrate that the free radical spin trap PBN reduces infarct size, even when given 1 or 3 h after the start of reperfusion, thus providing a second window of therapeutic possibility. A major effect of the drug is exerted on the recovery of energy metabolism of the tissue since it reduces a secondary deterioration in the bioenergetic state, occurring after 2–4 h of reperfusion. At least in part, the spin trap may exert its effect by reducing microvascular dysfunction caused by oedema and to adhesion of polymorphonuclear (PMN) leucocytes, which give rise to an inflammatory response mediated by cytokines, lipid mediators, or free radicals. This contention is supported by the reduction in focal ischaemic damage by antibodies to adhesion molecules for PMNs. However, it has now been found that the secondary deterioration of the bioenergetic state of core and penumbral tissues are mirrored by corresponding changes in the respiratory functions of isolated mitochondria, suggesting that, also in this type of ischaemia, the mitochondria suffer secondary damage. It is conceivable that a significant fraction of malfunctioning mitochondria emanate from microvascular tissue, explaining why antibodies to adhesion molecules mitigate the ischaemic lesions.

Forty-eight patients scheduled for elective cardiac surgery were randomly assigned to receive aprotinin in the following doses: 0.2 mg kg−1 (group A), 0.7 mg kg−1 (group B), 1 mg kg−1 (group C) and 1.4 mg kg−1 (group D). Clot formation was analysed by thromboelastography immediately after induction of anaesthesia and again 30 min after administration of aprotinin. Rate of clot formation was assessed using R (reaction time = rate of initial fibrin formation), K (clot formation time = rate of fibrin build-up and cross linking) and angle of clot formation (denoting speed at which solid clot forms). Strength of the clot was assessed by maximal amplitude of clot formation (MA)and % lysis after 30 and 60 min. Significant reduction of R and K times and increase in angle of clot formation was observed in groups A and B. This effect was not apparent in the other groups. In group D, an increase in R time was noted. These findings indicate a dose dependent effect of aprotinin on rate of clot formation with an earlier clot formation at low doses.

Continuous monitoring of body temperature during anaesthesia is a widely accepted clinical practice for which a variety of techniques are used. In this study, the accuracy of the deep body thermometer (Coretemp®) was compared with temperatures measured by needle thermocouples. With IRB approval and informed consent, seven ASA physical status I and II patients undergoing otolaryngeal surgery were studied. General anaesthesia and neuromuscular blockade were induced with thiamylal and vecuronium. Anaesthesia was maintained with isoflurane at an end-tidal concentration of 1.0–2.0% and 66% nitrous oxide in oxygen. After induction of general anaesthesia, subcutaneous temperature was measured at the sole of the left foot using a Coretemp®. Additionally, 8-, 18-, and 38-mm-long needle thermocouples were inserted into the the sole of the left foot close to Coretemp® and skin-surface temperature was also recorded adjacent to the needles. The Coretemp® measurement (Tc) correlated best with 18-mm-deep needle temperature (r2 = 0.87). There was also a good correlation between Tc and 38-mm-deep needle temperature (r2 = 0.83). Skin and 8-mm-deep needle temperatures correlated poorly or only moderately with Tc (r2 = 0.67, 0.75, respectively). These results indicate that temperatures measured by Coretemp® well reflect the temperatures at a depth of 18 mm or more from the skin into the foot.

In the past 10 years, the management of brain injury has shown several advances. Besides new diagnostic tools many new tentative approaches have been investigated, such as jugular bulb measurement of oxygen and lactate differences and near-infrared spectroscopy. The latest tool is microdialysis, which uses a probe as an interface to the brain. This method uses internally perfused semi-permeable membrane probes, which allow neurochemical water-soluble substances to be collected outside the brain for further analysis. Since the late 1980s the first results of microdialysis in neurointensive care show that chemical substances such as lactate, glucose, amino acids, metabolites of several biochemical mechanisms and electrolytes are measurable. This heterogeneous approach now waits for validation for clinical use and for the most challenging aspect, the clinical interpretation and use to improve therapy. The aim of this review is to describe the state of the art of this new technique, including our own experiences and concepts.

The most suitable time for tracheal intubation, following vecuronium 0.1 mg kg−1, was estimated in 120 patients. The trachea was intubated at cessation of the visually observed response of the orbicularis oculi muscle to facial nerve stimulation (group 1; n = 30), or of the manually detected response of the adductor pollicis to ulnar nerve stimulation (group 2; n = 30), or after waiting 3 min (group 3; n = 30), or 4 min (group 4; n = 30). There were no significant differences in intubation scores between the four groups of patients. Loss of response to train-of-four stimulation occurred significantly sooner in group 1 (orbicularis oculi) than in group 2 (adductor pollicis) P = 0.021). However, intubating conditions were poor in four patients (14%) in group 1, compared with none in group 2 and one in groups 3 and 4, respectively. Thus, contrary to expectations, the cessation of the response of the orbicularis oculi muscle did not guarantee good or even satisfactory intubating conditions. The results suggest that in fit adult patients it is as good to wait 3 min after injection of vecuronium 0.1 mg kg−1 before tracheal intubation, as to use a nerve stimulator.

Sufentanil or a sufentanil-clonidine combination was evaluated to determine whether the basal rate in patient-controlled epidural analgesia (PCEA) might affect the daily consumption, quality of analgesia or incidence of side effects. Following Caesarean section delivery, 60 patients were randomly assigned to receive one of the four following PCA regimens (15 patients per group) for the relief of post-operative pain by the epidural route: sufentanil 2μg mL−1 in 0.9% NaCl, demand dose 5μg i.e. 2.5mL, (group S+ with, group S without an infusion at 2.5mL hr−1) or sufentanil 2μg mL−1 + clonidine 3μg mL−1, demand dose 5μg sufentanil + 7.5μg clonidine i.e. 2.5mL (group SC+ with and SC without an infusion of 2.5ml hr−1). The other PCA settings (Bard I PCA pump) were a lock out interval of 10 min and a 1h limit of 20μg sufentanil and 30μg clonidine i.e. 10mL. The parameters measured were the analgesic drug consumption and number of dose demands during the first 24h, pain scores at 6h intervals, side effects and quality of sleep. The concurrent infusion increased the dose requirements regardless of the content of the syringe. Consumption of sufentanil was the highest in those patients receiving the plain solution with a basal infusion. Clonidine addition reduced the dose requirements but only significantly in those receiving the background infusion. Patients treated with the mixture tended to reach lower pain scores than those receiving sufentanil only without basal rate. Patients receiving the mixture with basal rate requested significantly fewer additional demands compared with the three other groups, but this did not influence the quality of sleep. Since side effects were more frequently registered in the patients in this group, it was concluded that the optimum regimen was the sufentanil-clonidine combination but with deletion of the basal rate.