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Summary: Peri‐operative medication safety is complex. Avoidance of medication errors is both system‐ and practitioner‐based, and many departments within the hospital contribute to safe and effective systems. For the individual anaesthetist, drawing up, labelling and then the correct administration of medications are key components in a patient's peri‐operative journey. These guidelines aim to provide pragmatic safety steps for the practitioner and other individuals within the operative environment, as well as short‐ to long‐term goals for development of a collaborative approach to reducing errors. The aim is that they will be used as a basis for instilling good practice. [ABSTRACT FROM AUTHOR]

Summary: The Earth's mean surface temperature is already approximately 1.1°C higher than pre‐industrial levels. Exceeding a mean 1.5°C rise by 2050 will make global adaptation to the consequences of climate change less possible. To protect public health, anaesthesia providers need to reduce the contribution their practice makes to global warming. We convened a Working Group of 45 anaesthesia providers with a recognised interest in sustainability, and used a three‐stage modified Delphi consensus process to agree on principles of environmentally sustainable anaesthesia that are achievable worldwide. The Working Group agreed on the following three important underlying statements: patient safety should not be compromised by sustainable anaesthetic practices; high‐, middle‐ and low‐income countries should support each other appropriately in delivering sustainable healthcare (including anaesthesia); and healthcare systems should be mandated to reduce their contribution to global warming. We set out seven fundamental principles to guide anaesthesia providers in the move to environmentally sustainable practice, including: choice of medications and equipment; minimising waste and overuse of resources; and addressing environmental sustainability in anaesthetists' education, research, quality improvement and local healthcare leadership activities. These changes are achievable with minimal material resource and financial investment, and should undergo re‐evaluation and updates as better evidence is published. This paper discusses each principle individually, and directs readers towards further important references. [ABSTRACT FROM AUTHOR]

This decision, and any subsequent surgery and anaesthesia, should be undertaken by senior staff in consultation with obstetric, neonatology, midwifery and obstetric anaesthetic teams. Identifying research priorities in anaesthesia and peri-operative care: final report of the joint National Institute of academic Anaesthesia/James Lind Alliance research priority setting partnership. Keywords: anaesthesia; complications; pre-natal EN anaesthesia complications pre-natal 143 146 4 01/10/23 20230201 NES 230201 Surgery for non-obstetric issues occurs in up to 1:100 pregnancies and can be an anxiety-provoking experience for the mother and healthcare staff, with concerns for maternal and fetal well-being [[1]]. Neurodevelopmental outcomes after prenatal exposure to anaesthesia for maternal surgery: a propensity-score weighted bidirectional cohort study. [Extracted from the article]

Which journals cite work published in anaesthetic journals is of potential interest to authors, editors and publishers. We analysed citations made in 2017-2018 for articles, reviews, editorials and letters published by 12 anaesthetic journals in 2016, using the Web of Science™ citation index platform. We analysed 12,544 citations made for 3518 items. Citations were most often made by specialist anaesthesia journals and critical care journals, and occurred most commonly in articles, followed by reviews, editorials and letters. The median (IQR [range]) number of citations made per item was 3.3 (2.6-4.1 [1.6-5.1]). The median (IQR [range]) number of journals that cited the 12 source journals was 302 (236-449 [139-671]). The median (IQR [range]) proportion of citations made by the same journal that published the items (i.e. 'self-citations') was 15% (11-17% [5-32%]). There were 1305/1932 (68%) citations made by North American journals for items published in North American journals and 1712/2063 (83%) citations made by European journals for items published in European journals, p < 0.0001. Our analysis may inform authors, editors and publishers where to submit work, what editorial policy to pursue and what journal strategy to follow, respectively. [ABSTRACT FROM AUTHOR]

The NHS Sustainable Development Unit has estimated that anaesthetic gases (including nitrous oxide) contribute ~5% of the carbon footprint of UK hospitals (~0.56/10.4 million tons CO SB 2 sb e; ~0.08 mt (~0.8%) inhalational anaesthetic agents only) [10]. 19 Al-Rifai Z, Mulvey D. Principles of total intravenous anaesthesia: practical aspects of using total intravenous anaesthesia. Anesthesia, inhalation, adverse effects, anesthesia, toxicity, air pollutants, environmental. [Extracted from the article]

Keywords: maternal outcomes; obstetric anaesthesia; process metrics; quality indicators EN maternal outcomes obstetric anaesthesia process metrics quality indicators 573 575 3 04/14/20 20200501 NES 200501 The aim of delivering high-quality clinical care that optimises patient outcomes has always been a driving principle in the practice of medicine. This shortcoming related to quality indicators, outlined above, is not unique; a systematic review of published studies of quality indicators in anaesthesia found that 64% were process indicators, and that patient-centred metrics accounted for the fewest published clinical indicators [1]. [Extracted from the article]

The article presents the consensus statement from the International Fragility Fracture Network Delphi on the principles of anaesthesia for hip fracture patients. It mentions that anaesthesia is an important part of multidisciplinary care of hip fracture patients. It offers information on the Fragility Fracture Network (FFN), organization for parctitioners, whoare interested in improving the standards of care for fragility fractures.

The author focuses on prospective clinical trial registration, a process in which clinical researchers publicize trial methodology details and conduct before participants are enrolled. Topics discussed include the purpose of prospectively registering a trial, such as increased transparency and decreased selective reporting about results; the role of journals in publication of clinical trial data; and the need for improving the consistency between trial registration and resulting articles.

The article discusses the guidelines used for the management of hypotension with vasopressors during caesarean section under spinal anaesthesia. It mentions that hypotension following combined or spinal spinal epidural anaesthesia at caesarean section causes both maternal and fetal/neonatal adverse effects. It also mentions that hypotension is a common consequence of the sympathetic vasomotor block caused by spinal anaesthesia.

Previous guidelines on consent for anaesthesia were issued by the Association of Anaesthetists of Great Britain and Ireland in 1999 and revised in 2006. The following guidelines have been produced in response to the changing ethical and legal background against which anaesthetists, and also intensivists and pain specialists, currently work, while retaining the key principles of respect for patients' autonomy and the need to provide adequate information. The main points of difference between the relevant legal frameworks in England and Wales and Scotland, Northern Ireland and the Republic of Ireland are also highlighted. [ABSTRACT FROM AUTHOR]

The authors discuss the artificial variation in anaesthetic practice for hip fracture surgery that results from a lack of evidence on which to base care. They cite the potential of continuous audit to determine whether adherence to the standards improves outcome compared with non-adherence if anaesthesia care for hip fracture is standardised nationally. The reduction of artificial variation in care and the achievement of high levels of safety and performance through standardisation is noted.

The author offers his view regarding the inaugural Featherstone Oration, Research not research – a rant in four acts, and Ireland's Winter Scientific Meeting that was held at the Association of Anaesthetists of Great Britain and in London, January 2016, respectively. He mentions that the his four area of concern about research such as precision in communications, absurd situation, and training programs in managing research.

Background: Current methods for verification of endotracheal intubation can fail, particularly in emergency settings. We investigated whether a verification method using electrical stimulation through electrodes placed on the endotracheal tube cuff could distinguish endotracheal and esophageal intubations in an experimental setting.Methods: During three sequential sessions simulating emergency intubation without paralysis, rapid sequence intubation (RSI) with neuromuscular blockade, and intubation during cardiopulmonary resuscitation, eight pigs were intubated with an endotracheal tube fitted with two electrodes exposed on the cuff of the tube, first in the esophagus and next in the trachea or in reverse sequence. Cuff pressure was monitored during a 5-s electrical stimulation (20 mA, 80 Hz, 500 μs), and delta pressure was calculated as the difference between baseline cuff pressure and maximum cuff pressure during the electrical stimulation.Results: Delta pressure was significantly higher in esophageal than in tracheal placements in all three sequential sessions (86.0 [78.3-89.7] vs. 6.5 [2.0-7.9] mmHg, P = 0.001; 16.6 [13.2-22.8] vs. 0.8 [0.3-2.6] mmHg, P = 0.004; 66.1 [60.0-84.7] vs. 2.7 [0.7-9.7] mmHg, P = 0.001). The delta pressure did not overlap between tracheal and esophageal intubations except for the session simulating RSI with neuromuscular blockade, in which one of eight esophageal placements showed a delta pressure within the delta pressure range of tracheal placements.Conclusion: Electrical stimulation through electrodes placed on the endotracheal tube cuff produced remarkably greater increases in cuff pressure in esophageal intubations than in tracheal intubations in an experimental setting. [ABSTRACT FROM AUTHOR]

We re-analysed prospective data collected by anaesthetists in the Anaesthesia Sprint Audit of Practice (ASAP-1) to describe associations with linked outcome data. Mortality was 165/11,085 (1.5%) 5 days and 563/11,085 (5.1%) 30 days after surgery and was not associated with anaesthetic technique (general vs. spinal, with or without peripheral nerve blockade). The risk of death increased as blood pressure fell: the odds ratio (95% CI) for mortality within five days after surgery was 0.983 (0.973-0.994) for each 5 mmHg intra-operative increment in systolic blood pressure, p = 0.0016, and 0.980 (0.967-0.993) for each mmHg increment in mean pressure, p = 0.0039. The equivalent odds ratios (95% CI) for 30-day mortality were 0.968 (0.951-0.985), p = 0.0003 and 0.976 (0.964-0.988), p = 0.0001, respectively. The lowest systolic blood pressure after intrathecal local anaesthetic relative to before induction was weakly correlated with a higher volume of subarachnoid bupivacaine: r(2) -0.10 and -0.16 for hyperbaric and isobaric bupivacaine, respectively. A mean 20% relative fall in systolic blood pressure correlated with an administered volume of 1.44 ml hyperbaric bupivacaine. Future research should focus on refining standardised anaesthesia towards administering lower doses of spinal (and general) anaesthesia and maintaining normotension. [ABSTRACT FROM AUTHOR]

The care of the elderly with hip fractures and their outcomes might be improved with resources targeted by the accurate calculation of risks of mortality and morbidity. We used a multicentre national dataset to evaluate and recalibrate the Nottingham Hip Fracture Score and Surgical Outcome Risk Tool. We split 9,017 hip fracture cases from the Anaesthesia Sprint Audit of Practice into derivation and validation data sets and used logistic regression to derive new model co-efficients for death at 30 postoperative days. The area (95% CI) under the receiver operator characteristic curve of 0.71 (0.67-0.75) indicated acceptable discrimination by the Nottingham Hip Fracture Score and acceptable calibration fit (Hosmer-Lemeshow test), p = 0.23, with a similar discrimination by the Surgical Outcome Risk Tool, 0.70 (0.66-0.74), which was miscalibrated to the observed data, p = 0.001. We recommend that studies test these scores for patients with hip fractures in other countries. We also recommend these models are compared with case-mix adjustment tools used in the UK. [ABSTRACT FROM AUTHOR]

The authors discuss the impact of the reports on anesthesia by the 5th National Audit Project (NAP5) and by the Mothers and Babies: Reducing Risk Through Audit and Confidential Enquiries Across the UK (MBRRACE-UK) on obstetric general anesthesia. Topics discussed include cases of awareness in obstetric anesthesia, recommendations of the reports for anaesthetists, and a forecast for general anaesthesia.

The authors comment on the study "Analgesic Efficacy of Pre-operative Stellate Ganglion Block on Postoperative Pain Relief: A Randomised Control Trial" published within the issue. The authors discuss the contributions of the study in terms of tramadol consumption administered to patients through analgesia, the methods of evaluating the benefits of analgesic intervention and ways by which the study has prompted a debate on whether including an invasive placebo in a clinical trial is appropriate.

Background Post-operative pain continues to be a major problem. Some previous studies have suggested that patients anaesthetised with propofol have less pain after surgery than those anesthetised with volatiles. However, the results of previous studies are conflicting. We designed a large-scale trial to study, whether propofol or sevoflurane is more analgesic than the other. We measured opioid consumption in the acute post-operative phase after laparoscopic hysterectomy. Methods In a randomised, prospective single-blind trial, we evaluated the consumption of oxycodone and pain intensity in 148 women for 20 h after laparoscopic hysterectomy under propofol or sevoflurane anaesthesia. The primary endpoint was the cumulative amount of oxycodone consumed. Secondary endpoints were pain scores [numeric rating scale ( NRS)] at rest and with coughing, severity of nausea and state of sedation. Results The consumption of oxycodone and the NRS pain scores did not differ between the groups. The oxycodone consumed during first 20 h after surgery was 42.5 (95% confidence interval 38.3-46.6) mg and 42.8 (37.3-48.4) mg in propofol- and sevoflurane-anaesthetised patients, respectively ( P = 0.919). NRS scores for nausea were higher in the patients receiving sevoflurane during the first 60 min in the post-anaesthesia care unit, leading to higher consumption of rescue antiemetics. Sedation scores differed in favour of sevoflurane only at 4 h time point after anaesthesia. Patient characteristics did not differ. Conclusions In this study, comparing sevoflurane with propofol for maintenance of general anaesthesia, the choice of anaesthetic had no effect on the requirement of oxycodone or intensity of pain after surgery. [ABSTRACT FROM AUTHOR]

Pilot and feasibility studies are preliminary investigations undertaken before a larger study. We hypothesised that only a small proportion of pilot or feasibility studies published in anaesthesia journals were correctly labelled as such. We searched for papers published between 2007 and 2017 in six anaesthesia journals using the text words 'pilot' OR 'feasibility' and included 266 original articles with 26,682 human participants. Only 34 (12.8%) were correctly labelled as a pilot or feasibility study. They were more likely to: have more median (IQR [range]) participants, 73 (40-130 [4-2716]) vs. 27 (15-60 [2-3305], p < 0.001; report feasibility outcomes, 82.4% vs. 4.3%, p < 0.001; and report an intention to convert, 100% vs. 39.7%, p < 0.001. They were less likely to test the efficacy of the primary outcome, 50% vs. 72.8%, p = 0.009; and report firm clinical conclusions 41.2% vs. 67.7%, p = 0.004. Of the studies published more than 5 years ago, correctly labelled pilot or feasibility studies were more likely to precede a published conversion study, 53.8% vs. 16%, p = 0.004. There was no difference between the number of citations 18 (9-44 [2-216]) vs. 20 (7-47 [0-251]), p = 0.865. These results have important consequences for patients, trialists, researchers and funders. We argue that correctly labelled pilot studies enhance the quality of scientific research by encouraging methodological rigour, ensuring scientific validity and reducing research waste. Authors, reviewers, editors and publishers should ensure they adhere to the contents of the 2016 CONSORT extension for pilot and feasibility studies. [ABSTRACT FROM AUTHOR]

We examined the prevalence of novel acronyms in the titles of anaesthetic and related studies and the response of anaesthetists to them. We separately analysed trainee-led research projects in the UK supported by the Research and Audit Federation of Trainees (RAFT), and a 10-year cohort of papers identified using the PubMed literature search tool. We also conducted a survey of 20 anaesthetists within our institution regarding the utility and impact of titles containing acronyms, and their recall of the associated topics. Finally, we developed a scoring system for acronym accuracy and complexity, the ORigin of AcroNym letterinG Used Term AppropriateNess (ORANGUTAN) score, and measured the progression of acronym usage over the 10-year period studied. Our results show that while acronyms themselves are sometimes considered memorable, they do not aid recall of topics and are, in general, not considered helpful. There has been an increase in the prevalence of acronymic titles over 10 years, and in the complexity of acronyms used, suggesting that there is currently a selective pressure favouring the use of acronyms even if they are of limited benefit. [ABSTRACT FROM AUTHOR]

The article offers information on a study concerning bone cement implantation syndrome (BCIS) that occurs in patients undergoing cemented prosthesis insertion for hip fracture repair. Topics discussed include a hypothesis on the association of anesthesia involving tracheal intubation with a reduced prevalence of clinically apparent BCIS; and the need to develop a cost-equivalent non-cemented prostheses to provide similar re-operation and mortality rates, and pain free mobility after surgery.

Background: Regional anaesthesia may have advantages in preserving immune function. Tumor-infiltrating lymphocytes (TILs) are considered indicators of immune response in the tumor microenvironment and used as a prognostic marker in patients after cancer surgery. This study investigated the effects of combined epidural anaesthesia on the number of TILs in patients undergoing surgery for lung adenocarcinoma.Methods: Patients undergoing radical resection for primary lung cancer were randomized to receive either combined epidural-general anaesthesia (Epi-GA) or general anaesthesia (GA) in an ongoing randomized controlled trial (ChiCTR-TRC-14004136). Excised adenocarcinoma specimens from patients enrolled between 1 June 2015 and 30 November 2015 were selected for immunohistochemical staining of CD8 and FOXP3 molecules. The numbers of positive lymphocytes were counted and expressed as the number of cells per mm2 tumor area.Results: One hundred and twenty-eight patients were recruited and randomized; 64 patients were included in immunohistochemistry analysis (37 received Epi-GA vs. 27 received GA). The number of CD8+ T cells was higher in the Epi-GA group than in the GA group (median [interquartile range]: 292.8 [198.0-418.3] vs. 204.7 [131.1-305.8], P = 0.036); whereas the number of FOXP3+ T cells was less in the Epi-GA group than in the GA group (37.6 [14.7-92.3] vs. 99.8 [68.9-168.3], P < 0.001).Conclusions: For patients undergoing surgery for lung adenocarcinoma under general anesthesia, use of epidural anaesthesia increased CD8+ T cells infiltration but decreased FOXP3+ T cells accumulation in tumor tissues. Epidural anaesthesia may affect TILs in a manner that preserves immune function. [ABSTRACT FROM AUTHOR]

We analysed data from the electronic rota system CLWRota, covering 2,689,962 anaesthetic sessions between 01/01/2014 and 31/12/2015, in 91 UK Trusts, in order to investigate trainees' supervision. There were 8209 trainee attachments analysed, during which 618,695 sessions were undertaken by trainees. The number of supervised sessions per week that trainees worked varied considerably (median (IQR [range]) 2.6 (1.6-3.6 [0-10]) for all grades combined), with senior trainees more likely than junior trainees to be supervised for fewer than the three sessions per week mandated by the Royal College of Anaesthetists. The number of supervised sessions was unrelated to Trusts' size, suggesting that trainees in smaller hospitals receive the same level of supervision as in larger teaching hospitals. Analysis of a dataset of this size should be a good reflection of the delivery of anaesthesia training in the UK. [ABSTRACT FROM AUTHOR]

Serious neurological lesions such as vertebral canal haematoma are rare after obstetric regional analgesia/anaesthesia, but early detection may be crucial to avoid permanent damage. This may be hampered by the variable and sometimes prolonged recovery following 'normal' neuraxial block, such that an underlying lesion may easily be missed. These guidelines make recommendations for the monitoring of recovery from obstetric neuraxial block, and escalation should recovery be delayed or new symptoms develop, with the aim of preventing serious neurological morbidity. [ABSTRACT FROM AUTHOR]

Neuraxial anaesthesia is widely used in obstetrics and neurological complications are rare. However, when they occur, subsequent investigation and management are time-critical and correlate with the extent of neurological recovery. The Third National Audit Project recommended the implementation of guidelines in obstetric epidural management, including advice on monitoring for early signs of problems and acting upon concerns. However, no national guideline exists for postoperative management in the obstetric population. We conducted a national survey of monitoring after obstetric neuraxial blockade and the management of an abnormally prolonged block. We received responses from 112/189 (59.3%) obstetric anaesthetic leads invited to participate. We determined that post-neuraxial blockade monitoring in the UK is highly variable: only 63/112 (56.3%) respondents' units had a monitoring policy in place, although most of these did not undertake formal neurological monitoring, and a range of different monitoring methods and schedules were employed. In 12/63 (19%) local policies, the first review of neurology was performed at the standard postoperative visit the following day, and 66/112 (58.9%) units had no protocol in place to address emergency management of abnormally prolonged neuraxial blockade. Where a policy was in place, the initial recommended action and the type of imaging used were variable. [ABSTRACT FROM AUTHOR]

Breastfeeding has many health benefits for the mother and infant. Women who are breastfeeding may require anaesthesia or sedation. Concerns regarding the passage of drugs into breast milk may lead to inconsistent advice from professionals. This can sometimes result in the interruption of feeding for 24 hours or longer after anaesthesia, or expressing and discarding ('pumping and dumping') breast milk; this may contribute to early cessation of breastfeeding. However, there are data regarding the transfer of most anaesthetic drugs into breast milk. We advise that breastfeeding is acceptable to continue after anaesthesia and should be supported as soon as the woman is alert and able to feed, without the need to discard breast milk. We provide evidence-based information on the pharmacokinetics of drugs commonly used during anaesthesia so that professionals can undertake a risk-benefit discussion with the woman. We advise the development of local policies that aid logistical planning and guide staff to facilitate breastfeeding during the woman's hospital stay. [ABSTRACT FROM AUTHOR]

A reply by the author on comments on his article on ultra-low dose intrathecal anaesthesia for hip fracture surgery is presented.

Intra-operative hypotension is a known predictor of adverse events and poor outcomes following major surgery. Hypotension often occurs on induction of anaesthesia, typically attributed to hypovolaemia and the haemodynamic effects of anaesthetic agents. We assessed the efficacy of fluid optimisation for reducing the incidence of hypotension on induction of anaesthesia. This prospective trial enrolled 283 patients undergoing radical cystectomy and randomly allocated them to goal-directed fluid therapy (n = 142) or standard fluid therapy (n = 141). Goal-directed fluid therapy patients received fluid optimisation based on stroke volume response to passive leg raise before induction; those with positive passive leg raise received intravenous crystalloid fluid boluses until stroke volume was optimised. Baseline mean arterial pressure was measured on the morning of surgery and on arriving in the operating theatre. This post-hoc analysis defined haemodynamic instability as either a > 30% relative drop in mean arterial pressure compared with baseline or absolute mean arterial pressure < 55 mmHg, within 15 min of induction. Forty-two (30%) goal-directed fluid therapy patients underwent fluid optimisation after finding an intravascular fluid deficit via passive leg raise testing; 106 (75%) goal-directed fluid therapy and 112 (79%) standard fluid therapy patients met criteria for haemodynamic instability. There was no significant difference in the incidence of haemodynamic instability between the goal-directed fluid therapy and standard fluid therapy groups using absolute mean arterial pressure drop below 55 mmHg (p = 0.58) or using pre-surgical testing or pre-surgical mean arterial pressure values as baseline (p = 0.21, p = 0.89, respectively); however, the difference in the incidence of haemodynamic instability was significant using the operating theatre baseline mean arterial pressure (p = 0.004). We conclude that fluid optimisation before induction of general anaesthesia did not significantly impact haemodynamic instability. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the 5th edition of the recommendations for standards of monitoring during anaesthesia and recovery by the Association of Anaesthetists of Great Britain and Ireland (AAGBI).

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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on the recommendations on accidental awareness under general anaesthesia in the fifth National Audit Project (NAP5).

Background and purpose Although several recent studies have implicated RYR1 mutations as a common cause of various myopathies and the malignant hyperthermia susceptibility ( MHS) trait, many of these studies have been limited to certain age groups, confined geographical regions or specific conditions. The aim of the present study was to investigate the full spectrum of RYR1-related disorders throughout life and to use this knowledge to increase vigilance concerning malignant hyperthermia. Methods A retrospective cohort study was performed on the clinical, genetic and histopathological features of all paediatric and adult patients in whom an RYR1 mutation was detected in a national referral centre for both malignant hyperthermia and inherited myopathies (2008-2012). Results The cohort of 77 non-related patients (detection rate 28%) included both congenital myopathies with permanent weakness and 'induced' myopathies such as MHS and non-anaesthesia-related episodes of rhabdomyolysis or hyper CKemia, manifested throughout life and triggered by various stimuli. Sixty-one different mutations were detected, of which 24 were novel. Some mutations are present in both dominant ( MHS) and recessive modes (congenital myopathy) of inheritance, even within families. Histopathological features included an equally wide spectrum, ranging from only subtle abnormalities to prominent cores. Conclusions This broad range of RYR1-related disorders often presents to the general paediatric and adult neurologist. Its recognition is essential for genetic counselling and improving patients' safety during anaesthesia. Future research should focus on in vitro testing by the in vitro contracture test and functional characterization of the large number of RYR1 variants whose precise effects currently remain uncertain. [ABSTRACT FROM AUTHOR]