A new understanding of the complex ways in which general anaesthetics act on the brain could eventually lead to improved drugs for surgery. | via Journal of Anaesthesia Practice
Although general anaesthesia is one of the most common medical procedures worldwide, it remains unclear how general anaesthesia works. In this research article, Professor Bruno van Swinderen, says his team had overturned previous understanding of what general anaesthetics do to the brain, finding the drugs did much more than induce sleep.
Propofol is the most commonly used general anesthetic in humans. Our understanding of its mechanism of action has focused on its capacity to potentiate inhibitory systems in the brain. However, it is unknown whether other neural mechanisms are involved in general anesthesia.
Here, we demonstrate that the synaptic release machinery is also a target. Using single-particle tracking photoactivation localization microscopy, we show that clinically relevant concentrations of propofol and etomidate restrict syntaxin1A mobility on the plasma membrane, whereas non-anesthetic analogs produce the opposite effect and increase syntaxin1A mobility.
Removing the interaction with the t-SNARE partner SNAP-25 abolishes propofol-induced syntaxin1A confinement, indicating that syntaxin1A and SNAP-25 together form an emergent drug target. Impaired syntaxin1A mobility and exocytosis under propofol are both rescued by co-expressing a truncated syntaxin1A construct that interacts with SNAP-25.
Our results suggest that propofol interferes with a step in SNARE complex formation, resulting in non-functional syntaxin1A nanoclusters.
The head of the CU School of Medicine Department of Anesthesiology in Colorado, has written a review of scientific studies on the potentially adverse effects of exposing developing brains to general anaesthesia | Anesthesiology
Recently, the U.S. Food and Drug Administration issued an official warning to all practicing physicians regarding potentially detrimental behavioral and cognitive sequelae of an early exposure to general anesthesia during in utero and in early postnatal life.
The U.S. Food and Drug Administration concern is focused on children younger than three years of age who are exposed to clinically used general anesthetics and sedatives for three hours or longer.
Although human evidence is limited and controversial, a large body of scientific evidence gathered from several mammalian species demonstrates that there is a potential foundation for concern. Considering this new development in public awareness, this review focuses on nonhuman primates because their brain development is the closest to humans in terms of not only timing and duration, but in terms of complexity as well.
McClelland, L. et al. | A national survey of the effects of fatigue on trainees in anaesthesia in the UK | Anaesthesia |2017; 72: 1069–77
Long shifts remain a major feature of working life for trainees in anaesthesia. Over the past 10 years, there has been an increase in awareness and understanding of the potential effects of fatigue on both the doctor and the patient. Despite the introduction of the European Working Time Directive into UK law, reducing the maximum hours worked by junior doctors, there is evidence that problems with inadequate rest and fatigue persist.
These authors conducted a national survey to assess the incidence and effects of fatigue among the 3772 anaesthetists in training within the UK.
A response rate of 59% was achieved, with data from 100% of NHS trusts. The results suggested that fatigue remains prevalent among junior anaesthetists, with 73.6% saying that it has effects on physical health, 71.2% that it affects psychological wellbeing and 67.9% that personal relationships are affected. The most problematic factor remains night shift work, with many respondents commenting on the absence of breaks, inadequate rest facilities and 57.0% stating that they had experienced an accident or near-miss when travelling home from night shifts.
The authors discuss potential explanations for the results, and present a plan to address the issues raised by their survey, aiming to change the culture around fatigue for the better.
The organisational state of inpatient pain management in UK hospitals is difficult to determine. We sent an electronic questionnaire to 209 acute pain service leads throughout the UK | Anaesthesia
Questions were about staffing and service provision. We received 141 responses (67%); 47% of all UK hospitals.
Each service was responsible for a median (IQR [range]) of 566 (400–839 [120–2800]) beds. Each acute pain specialist nurse was responsible for 299 (238–534 [70–1923]) beds. The mean (SD) number of consultant hours per week was 5.54 (4.62), delivered by a median of 1.0 (1.0–2.5 [0.2–7.0]) consultant. Overnight cover was provided by 20 (15%) acute pain services, and weekend cover by 39 (29%).
Acute pain services commonly (in 50 (35%) hospitals) had roles in addition to acute pain management. Most teams (105, (77%)) reviewed medical patients and patients with chronic pain (in 131, (96%) teams). Half of the services (56, (49%)), reported that they were part of an integrated acute and chronic pain service, however, 83 (59%) did not have any members who work in chronic pain clinics. The majority (79, (70%)) were able to access a nominated chronic pain consultant for advice.
Provision of acute pain services throughout the UK is highly variable. The majority do not meet core UK standards.
A systematic review including 34 trials with 3742 participants, identified through 6 database and supplementary searches | Anaesthesia
A multimedia format, alone or in combination with text or verbal formats, was studied in 20/34 (59%) trials: pre-operative anxiety was unaffected in 10 out of 14 trials and reduced by the multimedia format in three; postoperative anxiety was unaffected in four out of five trials in which formats were compared. Multimedia formats increased knowledge more than text, which in turn increased knowledge more than verbal formats. Other outcomes were unaffected by information format.
The timing of information did not affect pre-operative anxiety, postoperative pain or length of stay.
In conclusion, the effects of pre-operative information on peri-operative anxiety and other outcomes were affected little by format or timing.
Hinkelbein, J. et al. | European Society of Anaesthesiology and European Board of Anaesthesiology guidelines for procedural sedation and analgesia in adults | European Journal of Anaesthesiology
Procedural sedation and analgesia (PSA) has become a widespread practice given the increasing demand to relieve anxiety, discomfort and pain during invasive diagnostic and therapeutic procedures.
The European Society of Anaesthesiology (ESA) and the European Board of Anaesthesiology have created a taskforce of experts that has been assigned to create an evidence-based guideline and, whenever the evidence was weak, a consensus amongst experts on: the evaluation of adult patients undergoing PSA, the role and competences required for the clinicians to safely perform PSA, the commonly used drugs for PSA, the adverse events that PSA can lead to, the minimum monitoring requirements and post-procedure discharge criteria.
A search of the literature from 2003 to 2016 was performed by a professional librarian and the retrieved articles were analysed to allow a critical appraisal according to the Grading of Recommendations Assessment, Development and Evaluation method.
These guidelines contain recommendations on PSA in the adult population. It does not address sedation performed in the ICU or in children and it does not aim to provide a legal statement on how PSA should be performed and by whom. The National Societies of Anaesthesiology and Ministries of Health should use this evidence-based document to help decision-making on how PSA should be performed in their countries.
Schieren, M et al. Anaesthetic management of patients with myopathies. European Journal of Anaesthesiology | October 2017 | Volume 34 |Issue 10 | p 641–649
The anaesthetic management of patients with myopathies is challenging. Considering the low incidence and heterogeneity of these disorders, most anaesthetists are unfamiliar with key symptoms, associated co-morbidities and implications for anaesthesia.
The pre-anaesthetic assessment aims at the detection of potentially undiagnosed myopathic patients and, in case of known or suspected muscular disease, on the quantification of disease progression. Ancillary testing (e.g. echocardiography, ECG, lung function testing etc.) is frequently indicated, even at a young patient age.
One must differentiate between myopathies associated with malignant hyperthermia (MH) and those that are not, as this has significant impact on preoperative preparation of the anaesthesia workstation and pharmacologic management. Only few myopathies are clearly associated with MH.
If a regional anaesthetic technique is not possible, total intravenous anaesthesia is considered the safest approach for most patients with myopathies to avoid anaesthesia-associated rhabdomyolysis. However, the use of propofol in patients with mitochondrial myopathies may be problematic, considering the risk for propofol-infusion syndrome. Succinylcholine is contra-indicated in all patients with myopathies.
Following an individual risk/benefit evaluation, the use of volatile anaesthetics in several non-MH-linked myopathies (e.g. myotonic syndromes, mitochondrial myopathies) is considered to be well tolerated. Perioperative monitoring should specifically focus on the cardiopulmonary system, the level of muscular paralysis and core temperature. Given the high risk of respiratory compromise and other postoperative complications, patients need to be closely monitored postoperatively.