Regional analgesia for lower leg trauma and the risk of acute compartment syndrome: Guideline from the Association of Anaesthetists.

Pain resulting from lower leg injuries and consequent surgery can be severe. There is a range of opinion on the use of regional analgesia and its capacity to obscure the symptoms and signs of acute compartment syndrome. We offer a multi-professional, consensus opinion based on an objective review of case reports and case series. The available literature suggested that the use of neuraxial or peripheral regional techniques that result in dense blocks of long duration that significantly exceed the duration of surgery should be avoided. The literature review also suggested that single-shot or continuous peripheral nerve blocks using lower concentrations of local anaesthetic drugs without adjuncts are not associated with delays in diagnosis provided post-injury and postoperative surveillance is appropriate and effective. Post-injury and postoperative ward observations and surveillance should be able to identify the signs and symptoms of acute compartment syndrome. These observations should be made at set frequencies by healthcare staff trained in the pathology and recognition of acute compartment syndrome. The use of objective scoring charts is recommended by the Working Party. Where possible, patients at risk of acute compartment syndrome should be given a full explanation of the choice of analgesic techniques and should provide verbal consent to their chosen technique, which should be documented. Although the patient has the right to refuse any form of treatment, such as the analgesic technique offered or the surgical procedure proposed, neither the surgeon nor the anaesthetist has the right to veto a treatment recommended by the other.

Guidelines for safe transfer of the brain-injured patient: trauma and stroke, 2019: Guidelines from the Association of Anaesthetists and the Neuro Anaesthesia and Critical Care Society.

The location of care for many brain-injured patients has changed since 2012 following the development of major trauma centres. Advances in management of ischaemic stroke have led to the urgent transfer of many more patients. The basis of care has remained largely unchanged, however, with emphasis on maintaining adequate cerebral perfusion as the key to preventing secondary injury. Organisational aspects and training for transfers are highlighted, and we have included an expanded section on paediatric transfers. We have also provided a table with suggested blood pressure parameters for the common types of brain injury but acknowledge that there is little evidence for many of our recommendations. These guidelines remain a mix of evidence-based and consensus-based statements. We have received assistance from many organisations representing clinicians who care for these patients, and we believe our views represent the best of current thinking and opinion. We encourage departments to review their own practice using our suggestions for audit and quality improvement.

Guidelines for the safe provision of anaesthesia in magnetic resonance units 2019: Guidelines from the Association of Anaesthetists and the Neuro Anaesthesia and Critical Care Society of Great Britain and Ireland.

There has been an increase in the number of units providing anaesthesia for magnetic resonance imaging and the strength of magnetic resonance scanners, as well as the number of interventions and operations performed within the magnetic resonance environment. More devices and implants are now magnetic resonance imaging conditional, allowing scans to be undertaken in patients for whom this was previously not possible. There has also been a revision in terminology relating to magnetic resonance safety of devices. These guidelines have been put together by organisations who are involved in the pathways for patients needing magnetic resonance imaging. They reinforce the safety aspects of providing anaesthesia in the magnetic resonance environment, from the multidisciplinary decision making process, the seniority of anaesthetist accompanying the patient, to training in the recognition of hazards of anaesthesia in the magnetic resonance environment. For many anaesthetists this is an unfamiliar site to give anaesthesia, often in a remote site. Hospitals should develop and audit governance procedures to ensure that anaesthetists of all grades are competent to deliver anaesthesia safely in this area.

Differences between patients' and clinicians' research priorities from the Anaesthesia and Peri-operative Care Priority Setting Partnership.

The James Lind Alliance Anaesthesia and Peri-operative Care Priority Setting Partnership was a recent collaborative venture bringing approximately 2000 patients, carers and clinicians together to agree priorities for future research into anaesthesia and critical care. This secondary analysis compares the research priorities of 303 service users, 1068 clinicians and 325 clinicians with experience as service users. All three groups prioritised research to improve patient safety. Service users prioritised research about improving patient experience, whereas clinicians prioritised research about clinical effectiveness. Clinicians who had experience as service users consistently prioritised research more like clinicians than like service users. Individual research questions about patient experience were more popular with patients and carers than with clinicians in all but one case. We conclude that patients, carers and clinicians prioritise research questions differently. All groups prioritise research into patient safety, but service users also favour research into patient experience, whereas clinicians favour research into clinical effectiveness.

Recommendations for standards of monitoring during anaesthesia and recovery 2015: Association of Anaesthetists of Great Britain and Ireland.

This guideline updates and replaces the 4th edition of the AAGBI Standards of Monitoring published in 2007. The aim of this document is to provide guidance on the minimum standards for physiological monitoring of any patient undergoing anaesthesia or sedation under the care of an anaesthetist. The recommendations are primarily aimed at anaesthetists practising in the United Kingdom and Ireland. Minimum standards for monitoring patients during anaesthesia and in the recovery phase are included. There is also guidance on monitoring patients undergoing sedation and also during transfer of anaesthetised or sedated patients. There are new sections discussing the role of monitoring depth of anaesthesia, neuromuscular blockade and cardiac output. The indications for end-tidal carbon dioxide monitoring have been updated.

Peri-operative management of the surgical patient with diabetes 2015: Association of Anaesthetists of Great Britain and Ireland.

Diabetes affects 10-15% of the surgical population and patients with diabetes undergoing surgery have greater complication rates, mortality rates and length of hospital stay. Modern management of the surgical patient with diabetes focuses on: thorough pre-operative assessment and optimisation of their diabetes (as defined by a HbA1c < 69 mmol.mol(-1) ); deciding if the patient can be managed by simple manipulation of pre-existing treatment during a short starvation period (maximum of one missed meal) rather than use of a variable-rate intravenous insulin infusion; and safe use of the latter when it is the only option, for example in emergency patients, patients expected not to return to a normal diet immediately postoperatively, and patients with poorly controlled diabetes. In addition, it is imperative that communication amongst healthcare professionals and between them and the patient is accurate and well informed at all times. Most patients with diabetes have many years of experience of managing their own care. The purpose of this guideline is to provide detailed guidance on the peri-operative management of the surgical patient with diabetes that is specific to anaesthetists and to ensure that all current national guidance is concordant.

Role in host cell invasion of Trypanosoma cruzi-induced cytosolic-free Ca2+ transients.

Trypanosoma cruzi enters cells by a unique mechanism, distinct from phagocytosis. Invasion is facilitated by disruption of host cell actin microfilaments, and involves recruitment and fusion of host lysosomes at the site of parasite entry. These findings implied the existence of transmembrane signaling mechanisms triggered by the parasites in the host cells before invasion. Here we show that infective trypomastigotes or their isolated membranes, but not the noninfective epimastigotes, induce repetitive cytosolic-free Ca2+ transients in individual normal rat kidney fibroblasts, in a pertussis toxin-sensitive manner. Parasite entry is inhibited by buffering or depleting host cell cytosolic-free Ca2+, or by pretreatment with Ca2+ channel blockers or pertussis toxin. In contrast, invasion is enhanced by brief exposure of the host cells to cytochalasin D. These results indicate that a trypomastigote membrane factor triggers cytosolic-free Ca2+ transients in host cells through a G-protein-coupled pathway. This signaling event may promote invasion through modulation of the host cell actin cytoskeleton.

Local anaesthetics and adjuvants--future developments.

The introduction of local anaesthesia some years after the first public demonstration of general anaesthesia not surprisingly created less excitement and interest amongst both the public and the medical profession. However, in its own way, a new revolution was happening. Local anaesthesia produced an increase in the choice of anaesthetic techniques available to practitioners and patients. In common with general anaesthesia, the choice of agents remained very limited for the first six decades, and interest in the practice of local, regional or central neuraxial blockade and the development of new techniques and drugs were hampered by perceived safety issues even as late as the second half of the 20th century. It is only in the last few years that, with an apparent renaissance in the use of local anaesthesia, the pace of development has picked up. As the use and range of techniques has increased, so has interest in solving some of the longstanding problems with the available drugs.

Posttranscriptional control of embryonic rat skeletal muscle protein synthesis. Control at the level of translation by endogenous RNA.

The onset of muscle cell differentiation is associated with increased transcription of muscle-specific mRNA. Studies from this laboratory using 19-d embryonic rat skeletal muscle, suggest that additional, posttranscriptional controls regulate maturation of muscle tissue via a quantitative effect upon translation, and that the regulatory component may reside within the poly A- RNA pool (Nathanson, M.A., E.W. Bush, and C. Vanderburg. 1986. J. Biol. Chem. 261:1477-1486). To further characterize muscle cell translational control, embryonic and adult total RNA were separated into oligo(dT)cellulose-bound (poly A+) and -unbound (poly A-) pools. Unbound material was subjected to agarose gel electrophoresis to resolve constituents of varying molecular size and mechanically cut into five fractions. Material of each fraction was electroeluted and recovered by precipitation. Equivalent loads of total RNA from 19-20-d embryonic rat skeletal muscle exhibited a 40% translational inhibition in comparison to its adult counterpart. Inhibition was not due to decreased message abundance because embryonic, as well as adult muscle, contained equivalent proportions of poly A+ mRNA. An inhibition assay, based upon the translatability of adult RNA and its inhibition by embryonic poly A- RNA, confirmed that inhibition was associated with a 160-2,000-nt poly A- fraction. Studies on the chemical composition of this fraction confirmed its RNA composition, the absence of ribonucleoprotein, and that its activity was absent from similarly fractionated adult RNA. Rescue of inhibition could be accomplished by addition of extra lysate or mRNA; however, smaller proportions of lysate were required, suggesting a strong interaction of inhibitor and components of the translational apparatus. Additional studies demonstrated that the inhibitor acted at the level of initiation, in a dose-dependent fashion. The present studies confirm the existence of translational control in skeletal muscle and suggest that it operates at the embryonic to adult transition. A model of muscle cell differentiation, based upon transcriptional control at the myoblast level, followed by translational regulation at the level of the postmitotic myoblast and/or myotube, is proposed.

Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis.

To assess the effects of tauroursodeoxycholic acid (TUDCA) on bile excretory function, we examined whether TUDCA modulates vesicular exocytosis in the isolated perfused liver of normal rats in the presence of high (1.9 mM) or low (0.19 mM) extracellular Ca++ and in cholestatic rats 24 h after bile duct ligation. In addition, the effects of TUDCA on Ca++ homeostasis were compared in normal and in cholestatic hepatocytes. In the isolated perfused rat liver, TUDCA (25 microM) stimulated a sustained increase in the biliary excretion of horseradish peroxidase, a marker of the vesicular pathway, in the presence of high, but not low extracellular Ca++ or in the cholestatic liver. In contrast, TUDCA stimulated bile flow to the same extent regardless of the concentration of extracellular Ca++ or the presence of cholestasis. In indo-1-loaded hepatocytes, basal cytosolic free Ca++ ([Ca++]i) levels were not different between normal and cholestatic cells. However, in cholestatic cells [Ca++]i increases induced by TUDCA (10 microM) and its 7 alpha-OH epimer taurochenodeoxycholic acid (50 microM) were reduced to 22% and 26%, respectively, compared to normal cells. The impairment of TUDCA-induced [Ca++]i increase in cholestatic cells could be mimicked by exposing normal cells to low extracellular Ca++ (21%) or to the Ca++ channel blocker NiCl2 (23%). These data indicate that (a) dihydroxy bile acid-induced Ca++ entry may be of functional importance in the regulation of hepatocellular vesicular exocytosis, and (b) this Ca++ entry mechanism across the plasma membrane is impaired in cholestatic hepatocytes. We speculate that the beneficial effect of ursodeoxycholic acid in cholestatic liver diseases may be related to the Ca+(+)-dependent stimulation of vesicular exocytosis by its conjugate.

Stimulation of bile duct epithelial secretion by glybenclamide in normal and cholestatic rat liver.

Cholestasis is a cardinal complication of liver disease, but most treatments are merely supportive. Here we report that the sulfonylurea glybenclamide potently stimulates bile flow and bicarbonate excretion in the isolated perfused rat liver. Video-microscopic studies of isolated hepatocyte couplets and isolated bile duct segments show that this stimulatory effect occurs at the level of the bile duct epithelium, rather than through hepatocytes. Measurements of cAMP, cytosolic pH, and Ca2+ in isolated bile duct cells suggest that glybenclamide directly activates Na+-K+-2Cl- cotransport, rather than other transporters or conventional second-messenger systems that link to secretory pathways in these cells. Finally, studies in livers from rats with endotoxin- or estrogen-induced cholestasis show that glybenclamide retains its stimulatory effects on bile flow and bicarbonate excretion even under these conditions. These findings suggest that bile duct epithelia may represent an important new therapeutic target for treatment of cholestatic disorders.

Coordination of hormone-induced calcium signals in isolated rat hepatocyte couplets: demonstration with confocal microscopy.

Excitable cells often display rapid coordination of hormone-induced intracellular calcium signals. Calcium elevations that begin in a single epithelial cell also may spread to adjacent cells, but coordination of hormone-induced signals among epithelial cells has not been described. We report the use of confocal microscopy to determine the inter- and intracellular distribution of cytosolic calcium in isolated rat hepatocyte couplets, an isolated epithelial cell system in which functional polarity is maintained. Both vasopressin and phenylephrine evoked sequential coordinated calcium signals in the couplets, even during cytosolic calcium oscillations. The coupling was abolished by closure of intercellular gap junction channels by treatment with octanol. These observations demonstrate that hormone-induced intracellular calcium signals are coordinated among hepatocytes and suggest that gap junction channels mediate this intercellular integration of tissue responsiveness.