General Anesthetic Research Articles

A randomized, controlled trial on the effect of anesthesia on chronic pain after total knee arthroplasty.

Aim: The study sought to evaluate the influence of anesthesia on chronic pain after total knee arthroplasty (TKA). Methods: This was a single-center, randomized controlled study, with patients receiving a spinal anesthetic (SP) alone or a general anesthetic (GA) with femoral block, with follow-up at 3 and at 6 months. The primary outcome was the WOMAC® score at 6months. Results: 199 patients were enrolled. Group SP had better function (WOMAC: GA: 16.9 vs SP: 14.4, p =0.015) and less pain (WOMAC pain: GA: 3.04 vs SP: 2.69, p =0.02) at 3 months, but not at6months. Overall, 11% of patients had chronic postsurgical pain (CPSP), with Group GA having a higher incidence of CPSP at 6months. Neuropathic pain increased during the follow-up and was more common in patients with CPSP. Conclusion: An SPreduces pain and incidence of CPSP after TKA. Clinical Trial Registration: NCT04206046 (ClinicalTrials.gov).

Differential assembly diversifies GABAA receptor structures and signalling.

Type A γ-aminobutyric acid receptors (GABAARs) are pentameric ligand-gated chloride channels that mediate fast inhibitory signalling in neural circuits1,2 and can be modulated by essential medicines including general anaesthetics and benzodiazepines3. Human GABAAR subunits are encoded by 19 paralogous genes that can, in theory, give rise to 495,235 receptor types. However, the principles that govern the formation of pentamers, the permutational landscape of receptors that may emerge from a subunit set and theeffect that this has on GABAergic signalling remain largely unknown. Here we use cryogenic electron microscopy to determine the structures of extrasynaptic GABAARs assembled from α4, β3 and δ subunits, and their counterparts incorporating γ2 instead of δ subunits. In each case, we identified two receptor subtypes with distinct stoichiometries and arrangements, all four differing from those previously observed for synaptic, α1-containing receptors4-7. This, in turn, affects receptor responses to physiological and synthetic modulators by creating or eliminating ligand-binding sites at subunit interfaces. We provide structural and functional evidence that selected GABAAR arrangements can act as coincidence detectors, simultaneously responding to two neurotransmitters: GABA and histamine. Using assembly simulations and single-cell RNA sequencing data8,9, we calculated the upper bounds for receptor diversity in recombinant systems and in vivo. We propose that differential assembly is a pervasive mechanism for regulating the physiology and pharmacology of GABAARs.

Cohen’s Comprehensive Thoracic Anesthesia

Cohen’s Comprehensive Thoracic Anesthesia

Anesthetic Preconditioning of Traumatic Brain Injury Is Ineffective in a Drosophila Model of Obesity.

We tested the hypothesis that obesity influences the pharmacodynamics of volatile general anesthetics (VGAs) by comparing effects of anesthetic exposure on mortality from traumatic brain injury (TBI) in lean and obese Drosophila melanogaster We induced TBI with a high-impact trauma device. Starvation-selection over multiple generations resulted in an obese phenotype (SS flies). Fed flies served as lean controls (FC flies). Adult (1-8-day-old) SS and FC flies were exposed to equianesthetic doses of isoflurane or sevoflurane either before or after TBI. The principal outcome was percent mortality 24 hours after injury, expressed as the Mortality Index at 24 hours (MI24). TBI resulted in a lower MI24 in FC than in SS flies [21 (2.35) and 57.8 (2.14), respectively n = 12, P = 0.0001]. Pre-exposure to isoflurane or sevoflurane preconditioned FC flies to TBI, reducing the risk of death to 0.53 (0.25 to 1.13) and 0.82 (0.43 to 1.58), respectively, but had no preconditioning effect in SS flies. Postexposure to isoflurane or sevoflurane increased the risk of death in SS flies, but only postexposure to isoflurane increased the risk in FC flies [1.39 (0.81 to 2.38)]. Thus, obesity affects the pharmacodynamics of VGAs, thwarting the preconditioning effect of isoflurane and sevoflurane in TBI. SIGNIFICANCE STATEMENT: Inadvertent preconditioning in models of traumatic brain injury (TBI) is a recognized confounder. The findings in a fruit fly (Drosophila melanogaster) model of closed-head TBI indicate that anesthetic pharmacodynamics are profoundly affected by obesity. Specifically, obesity thwarts the brain-protective effect of anesthetic preconditioning. This finding is important for experimental studies of TBI and supports the versatility of the fruit fly as a model for the exploration of anesthetic pharmacodynamics in a wide parameter space.

Complications associated with paediatric airway management during the COVID-19 pandemic: an international, multicentre, observational study.

SummaryRespiratory adverse events in adults with COVID‐19 undergoing general anaesthesia can be life‐threatening. However, there remains a knowledge gap about respiratory adverse events in children with COVID‐19. We created an international observational registry to collect airway management outcomes in children with COVID‐19 who were having a general anaesthetic. We hypothesised that children with confirmed or suspected COVID‐19 would experience more hypoxaemia and complications than those without. Between 3 April 2020 and 1 November 2020, 78 international centres participated. In phase 1, centres collected outcomes on all children (age ≤ 18 y) having a general anaesthetic for 2 consecutive weeks. In phase 2, centres recorded outcomes for children with test‐confirmed or suspected COVID‐19 (based on symptoms) having a general anaesthetic. We did not study children whose tracheas were already intubated. The primary outcome was the incidence of hypoxaemia during airway management. Secondary outcomes included: incidence of other complications; and first‐pass success rate for tracheal intubation. In total, 7896 children were analysed (7567 COVID‐19 negative and 329 confirmed or presumed COVID‐19 positive). The incidence of hypoxaemia during airway management was greater in children who were COVID‐19 positive (24 out of 329 (7%) vs. 214 out of 7567 (3%); OR 2.70 (95%CI 1.70–4.10)). Children who had symptoms of COVID‐19 had a higher incidence of hypoxaemia compared with those who were asymptomatic (9 out of 51 (19%) vs. 14 out of 258 (5%), respectively; OR 3.7 (95%CI 1.5–9.1)). Children with confirmed or presumed COVID‐19 have an increased risk of hypoxaemia during airway management in conjunction with general anaesthesia.

Major complications of airway management: a prospective multicentre observational study.

We conducted an observational study of serious airway complications, using similar methods to the fourth UK National Audit Project (NAP4) over a period of 1 year across four hospitals in one region in the UK. We also conducted an activity survey over a week, using NAP4 methods to yield an estimate for relevant denominators to help interpret the primary data. There were 17 serious airway complications, defined as: failed airway management leading to cancellation of surgery (eight); airway management in recovery (five); unplanned intensive care admission (three); and unplanned emergency front of neck access (one). There were no reports of death or brain damage. This was an estimate of 0.028% (1 in 3600) complications using the denominator of 61,000 general anaesthetics per year in the region. Complications in patients with 'predicted easy' airways were rare (approximately 1 in 14,200), but 45 times more common in those with 'predicted difficult' airways (approximately 1 in 315). Airway management in both groups was similar (induction of anaesthesia followed by supraglottic airway or tracheal tube). Use of awake/sedation intubation, videolaryngoscopy and high-flow nasal oxygenation were uncommon even in the predicted difficult airway patients (in 2.7%, 32.4% and 9.5% of patients, respectively). We conclude that the incidence of serious airway complications is at least as high as it was during NAP4. Despite airway prediction being used, this is not informing subsequent management.

Suspected pulmonary oedema development in a pig following general anaesthesia and the associated complications encountered during a subsequent general anaesthetic

AbstractAn 85 kg, 6‐year‐old pig presenting with stranguria was anaesthetised for computed tomography and cystotomy. During this anaesthetic, bradyarrhythmias occurred twice, both responding to medical intervention. A cystotomy tube was placed but the removal of one urethrolith was not possible. Recovery from anaesthesia was uneventful. During hospitalisation, the animal's respiratory rate and effort increased, with crackles on thoracic auscultation. As this responded to antibiotics and a reduction in intravenous fluid therapy, the pig underwent a second anaesthetic for a percutaneous cystolithotomy to remove the urethrolith. On induction of anaesthesia, clear fluid was visible in the oropharynx. This was removed by suction but after intubation large volumes flowed from the respiratory tract via the endotracheal tube. The pig's condition was stabilised during the anaesthetic with intravenous furosemide and intermittent positive‐pressure ventilation. Surgery was completed and the animal recovered from anaesthesia. Postoperatively the pig developed severe dyspnoea and cardiopulmonary arrest.

Addressing the need for patient-friendly medical communications: adaptation of the 2019 recommendations for the management of MPS VI and MPS IVA

BackgroundPatients are the most important stakeholders in the care of any disease and have an educational need to learn about their condition and the treatment they should receive. Considering this need for patient-focused materials, we present a directed approach for mucopolysaccharidosis (MPS) VI and MPS IVA, a pair of rare, inherited diseases that affects multiple organs and parts of the body. Independent guidelines on the treatment of these diseases were recently published, providing evidence- and expertise-driven recommendations to optimize patient management. However, while healthcare providers may have the training and knowledge to understand these guidelines, patients and their caregivers can find the technical content challenging. Hence, we aimed to develop plain language summaries (PLS) of the MPS VI and MPS IVA guidelines with patients as the primary audience.ResultsA review of the guidelines by an expert team identified six domains of information relevant to patients: The multidisciplinary team, regular tests and check-ups, disease-modifying and supportive treatments, general anesthetics, ear-nose-throat/respiratory care, and surgeries. This information was adapted into a series of infographics specific to either MPS VI or MPS IVA, designed to appeal to patients and clearly present information in a concise manner.ConclusionsThe use of patient-friendly materials, like the infographics we have developed, has the potential to better inform patients and engage them in their care. We issue a “call to arms” to the medical community for the development of similar PLS materials in rare diseases intended to inform and empower patients.

Sub-epidermal moisture versus traditional and visual skin assessments to assess pressure ulcer risk in surgery patients.

To compare the predictive ability of subepidermal moisture (SEM) measurement versus traditional risk assessment and visual skin assessment (VSA) as means of detecting early pressure ulcer (PU) damage development among adults undergoing surgery. A non-experimental, comparative, descriptive cohort study design was used. Following ethical approval, participants who had given their informed written consent had their skin assessed over the areas that were weight-bearing during surgery, using VSA and the SEM measurement. Visual PUs were graded according to the European Pressure Ulcer Advisory Panel and National Pressure Ulcer Advisory Panel ulcer grading system. Assessments took place preoperatively, then daily on the ward, beginning on day one postoperatively and continuing for three days or until discharge. Of the 231 participants, who had a mean age of 57.50 years, 55.8% (n=129) were male. The most common comorbidity was cardiology/vascular (n=42; 18.2%). Just over half (52.4%; n=121) underwent orthopaedic surgery and 47.6% (n=110) underwent non-orthopaedic surgery; 70% (n=163) received a general anaesthetic and 43% (n=100) were in the supine decubitus position during surgery. PU incidence was 51% (n=116), according to SEM measurement, and 3% (n=7) according to VSA. Among the seven participants who developed a visual PU, 10 PUs at stage 1 developed (31%); some patients developed more than one PU. Of the participants who had assessments for three days postoperatively, 94% (n=61) had a persistently high SEM delta on day three. The variables that emerged as statistically significantly related to abnormal SEM measurement deltas among these participants were: surgery duration (p=0.038); having orthopaedic surgery (p=0.020); supine surgical position (p=0.003); spinal anaesthetic type (p=0.0001); and Waterlow and Braden mobility subscale day one postoperatively (p=0.0001). None of the variables had a statistically significant influence on abnormal VSA. Surgical patients, because of immobility, are vulnerable to the action of compression and shear forces. These forces cause changes at a cellular level that trigger inflammation, which is a precursor to early tissue damage. SEM measurement can detect this tissue damage from the increase in the underlying tissue water content that results from inflammation. From the findings of this study, SEM measurement is very promising in the detection of early tissue damage in those at risk of PU development among the surgical population.

Development and initial testing of valves opened by Valsalva (abdominal straining): Proof of principle for urinary catheters or male urethra

We hypothesised that raising the abdominal pressure could provide a non-manual approach to opening a urinary valve, with potential application for indwelling catheters or an intraurethral device. The ‘Vysera’ valve remains closed during short high amplitude spikes but opens when a pre-defined low-amplitude pressure is maintained for a pre-specified duration, allowing sustained abdominal straining to achieve voluntary opening. The valve was subjected to in vitro performance and microbiological tests. Parameters for valve specification were selected by review of a large urodynamic database with nominal opening pressure of 75 cmH2O ＋/−15 cmH2O (range 60–90 cmH2O) and valve pressure was refined using early clinical results. Valve housings were designed for the end of a Foley catheter, and for male post-prostatectomy intraurethral placement. Preliminary clinical evaluation was undertaken for both designs, incorporating qualitative feedback. In vitro testing of the catheter valve demonstrated only minimal encrustation. On clinical evaluation of the catheter-sited valve, six of seven patients (86%) were able to open the valve intentionally by straining. When inactive, none of the patients experienced leakage (7/7 = 100%), while five (71%) leaked when they coughed. The intraurethral device was successfully placed with image intensifier guidance under general anaesthetic in five of nine patients. Three patients used the device; initial leakage resolved as patients mobilised. However, in contrast to the catheter-sited valve, the intraurethral device was difficult to tolerate for even a few hours. Removal was performed under local anaesthesia with a flexible cystoscope and stent grasper. We conclude that storage and bladder emptying using a strain-activated valve are feasible for a catheter valve and an intra-urethral device. The valve parameters need to be matched to individual patients. For the intraurethral device, additional development is needed to improve the stent housing and valve performance.

A hypothesis concerning distinct schemes of olfactory activation evoked by perceived versus nonperceived input

SignificanceThe authors propose that odors are consciously perceived or not, depending on whether the olfactory cortex succeeds in activating the endopiriform nucleus-a structure that, in turn, is capable of activating multiple downstream brain areas. The authors further propose that the cellular mechanisms of endopiriform nucleus activation are an attenuated form of cellular events that occur during epileptic seizure initiation. If correct, the authors' hypothesis could help explain the mechanisms of action of certain general anesthetics.

Amino acids versus magnesium sulfate infusion for controlling postoperative shivering in patients undergoing percutaneous nephrolithotomy surgery: a randomized clinical trial.

General anesthetics disrupt the thermoregulatory mechanisms by reducing vasoconstriction and shivering thresholds. Postoperative shivering is a challenging anesthesia-related complication with an incidence range of 20-70%. Amino acids that induce thermogenesis and magnesium sulfate are centrally acting mechanisms that could minimize shivering. Thus, this trial was designed to compare the effect of amino acid versus magnesium sulfate infusion on postoperative shivering in patients undergoing elective percutaneous nephrolithotomy (PCNL) surgery under general anesthesia. Eighty adults, American Society of Anesthesiologists I and II patients, were randomly assigned into one of two groups. Group A received general anesthesia and perioperative IV amino acid infusion. Group M received general anesthesia and perioperative IV magnesium sulfate infusion. There was a statistically significant difference in shivering score, which was lower in group A than M (0.8±1.1 versus 1.5±1.3; P value=0.01). The incidence of postoperative shivering was lower in group A (4 [10%]) versus (11 [27.5%]) in group M. A less decrease in the core intraoperative temperature (Celsius) was observed in group A than in group M (35.5±0.2 versus 35.1±0.2; respectively, P<0.001) and at the end of surgery (36.1±0.3 versus 35.7±0.3; respectively, P<0.001). Perioperative amino acids infusion is more effective and better tolerated than magnesium sulfate in preventing postoperative shivering in patients undergoing percutaneous nephrolithotomy surgery. Cost effectiveness should be kept in mind, and amino acids infusion should be reserved in high-risk surgeries for shivering.

Introducing Ethanol Ablation as a treatment for thyroid cysts in the emergency setting

Abstract Introduction New techniques have been adopted for minimally invasive management of thyroid lesions which has been well explored by Nixon et al. Ethanol ablation (EA) for the treatment of thyroid cysts has been well documented in the literature as a safe, effective treatment option in the elective setting. Our unit has introduced this service in the elective setting for treatment of thyroid cysts. This study demonstrates the use of EA in the emergency setting, which has potential to reduce recurrence rates and avoid a general anaesthetic in patients who present acutely. Methods Three patients presenting with airway threatening compressive symptoms secondary to thyroid cysts. Treated with EA within 24 hours of presentation to hospital. Patients were followed up radiologically and clinically and a telephone consultation to gather the GBI (Glasgow Benefit Inventory) survey. Results 2 patients female and 1 male, median age of 41 years old. Median Pre-ablation cyst volume was 97.3mls. Median 100% radiological resolution of cystic component. 100% resolution of symptoms at median 9-month follow-up post procedure. 66% of patients requiring only one treatment for 100% resolution, with 1 patient with the largest cyst requiring three ablations and two aspirations. No complications reported. GBI (Glasgow Benefit Inventory) score mean +27.7, similar GBI of a tonsillectomy. Discussion EA is a safe, cost effective and efficient treatment option for thyroid cysts in the acute setting. Larger thyroids cysts may require repeated procedures for symptom resolution. Patient will require long term follow up to assess the rate of recurrence.

49 Accurate Hip Reduction and SPICA Application for DDH – the Case for Intraoperative CT

Abstract Aim Accurate reduction of the hip joint and SPICA application for treatment of developmental dysplasia of the hip (DDH) is crucial for long term success – for those undergoing surgical intervention, or closed reduction only. In Alder Hey Children’s Hospital we compared two methods of confirming reduction for patients undergoing SPICA application for DDH. Those receiving either post-operative departmental computed tomography (CT) or an intra-operative CT. Specific outcome assessed were, need for repeat CT and SPICA application, return to theatre (RTT), repeat general anaesthetic (GA) (with associated risks), as well as effect on overall length of stay (LOS). Method Patient lists were attained from the radiography department, information regarding RTT and LOS were derived from Meditech V6. CT scans were checked on PACS imaging system. Results Retrospective analysis of all SPICA application cases performed, included 102 patients from 2015–2018 undergoing a departmental CT, after GA. Of these, 6 patients required a second GA, 1 patient required 3 GA’s. Mean LOS was 6 days in those requiring repeat SPICA application. Analysis of the second group of intra-operatively CT scanned patients, included 72 patients from 2018–2020. Of these, 0 patients required a repeat GA and RTT, despite 1 patient requiring change of SPICA. Mean LOS was 4 days for these patients. Conclusions Intra-operative CT is crucial for getting it right first time, reducing risks of GA and cost of theatre time. It reduced the LOS for those requiring SPICA change from 6 to 4 days and reduced mean LOS by 1 day overall.

61 Use of Ketamine Sedation for the Treatment of Minor Plastic Surgery Procedures in the Paediatric Emergency Department

Abstract Aim To determine if ketamine sedation is a safe and cost-effective way of treating paediatric patients presenting with minor injuries, requiring plastic surgery procedures, in the emergency department. Method A retrospective cohort study was carried out over a 9-month period in children between ages 18 months and 16 years old, presenting to the paediatric emergency department at Chelsea and Westminster Hospital with minor injuries requiring plastic surgery input. The data collected included previously validated co-primary outcome measures of surgical site infection at 7 days and cosmetic appearance summary score at a minimum of 4 months. Parental satisfaction surveys were completed at 4 months to assess perceived quality of treatment. A cost analysis comparison against procedures completed under general anaesthetic was also undertaken. Results During the 9-month period of study, 24 minor procedures were performed under ketamine in the paediatric emergency department. There were no serious adverse events recorded. Three cases exceeded the recommended 20-minute maximum procedure duration, but there was no associated adverse outcome. No cases required further procedures under general anaesthesia and there were no cases of surgical site infections at 7 days. Parents reported extremely favourable outcomes using this technique, with an average overall satisfaction score of 9.2 (assessed over a number of parameters, where 10 is complete satisfaction). Conclusions Ketamine procedural sedation in the paediatric population is a safe and cost-effective method for the treatment of minor plastic surgery procedures, with low risk for surgical site infection post-operatively, and high parent satisfaction rates

112 Improving Neonatal Vascular Access in Surgical Patients

Abstract Aim Many neonatal surgical patients require intravenous (IV) access for &amp;gt;1 week. Technical, organisational, and cultural factors reduced placement of peripherally inserted central catheters (PICCs). Most babies requiring parenteral nutrition/central medications undergo central venous line placement under general anaesthetic (GA). Repeated bedside cannulation causes distress to patients and parents, with workload burden resulting in extravasation injuries. We aim to reduce these factors by increasing PICC usage in a ward setting. Method We followed a Plan, Do, Study, Act cycle over 4 months. Results Final results pending. The intervention has occurred, in 1 month we will re-measure: We will measure risks of increasing PICC placement (through an iterative process), including: Conclusions The initial message yielded perceptions that ‘the department is doing things wrong’. The message of PICCs adding an ‘extra string to our bow’ was clearer, non-judgemental and with strong rationale for change. Training non-rotating staff promotes sustainability but required senior clinician agreement to procure equipment, delaying our timeline – target completion is in 1 month.

312 Foreign Bodies in the Urinary Tract - Can We Learn Something from the Pandemic?

Abstract Aim We aim to quantify the morbidity and resource utilisation from patients presenting with foreign bodies in the urinary tract and analyse the effect of the coronavirus pandemic on the numbers. Often these patients have co-existing mental health issues, which necessitates coordinated multi-disciplinary care. It is important that patient care is assessed holistically, with assessment of whether changes in mental health care impact urological morbidity. Method We performed a 2-year, retrospective, single-institution study of patients requiring removal of foreign bodies from their urinary tract. Results There were 49 episodes of patients needing removal of foreign body; all were inpatients at the regional mental health hospital.8% of patient episodes presented with urinary sepsis. All patients had successful general anaesthetic, endoscopic removal of the foreign body from their urinary tract. There was significantly more episode’s pre-pandemic (38 episodes, mean 2.7 per month) than during the pandemic (11 episodes, mean 1.1 per month). During the pandemic, staffing levels within the mental health hospital have been increased to enable isolation procedures to be conducted when necessary. It was felt that the reduction in foreign body insertion episodes was a consequence of this. The resultant reduction in acute hospital admissions and procedures is estimated to have saved £400,256 per annum. Conclusions Patients presenting with a foreign body in the urinary tract utilize a considerable number of resources and are a source of morbidity. Urosepsis and retention are common sequelae. Reduced episodes during the pandemic have shown that increased staffing levels have a positive effect and could be cost-effective. It is imperative that this data is used to appropriately allocate resources to reduce patient morbidity.

The impact of parity in primary breast augmentation: A clinical and cost-effective case control study

Breast augmentation is one of the most commonly performed aesthetic procedures in women. Despite the structural changes which occur during pregnancy and lactation have been extensively studied, there is no clarity in terms of the time required for the parenchymal angiogenic changes to regress or if these neovessels are preserved even years after the last lactating period. This study investigated whether these post-pregnancy structural changes on the breasts may influence the surgical efficiency, affect the rates of complications and have an impact on cost-effectiveness in primary breast augmentation. This study encompasses a retrospective review of all patients who underwent implant-based bilateral primary breast augmentation, through inframammary fold (IMF) incision under general anaesthetic, by a single surgeon. The age, height, weight and parity (nulliparous or multiparous status), characteristics of implants used and clinical outcomes after a minimum of 6-month post-operative follow-up were recorded. A further prospective comparative trial investigated the effects of parity in the surgical efficiency and cost-effectiveness in primary breast augmentation. The surgical efficiency (total operative time) and the immediate complications of 85 consecutive cohort of patients were recorded by an independent observer. Statistical correlation investigated the relevance of parity as predictors of surgical efficiency and cost-effectiveness. A total of 894 patients were included with a minimum of 6-month follow-up following implants-based primary breast augmentation. There were 445 (49.8%) nulliparous and 449 (50.2%) patients had at least one child at the time of surgery. The average parity index was calculated to be 1.05. The average body mass index (BMI) was 20.8kg/m2 (15.9-30.8). The mean implant volume used was 314ml. Fifteen percent (n=134) presented with post-operative complications, with an average follow-up period of 12.8 (6-116) months. The differences between parity and incidence of complications were not statistically significant (p=0.82). Surgical efficiency parameters from 85 women (54 multiparous and 31 nulliparous) demonstrated total operative time difference; 35±6.3min for multiparous and 30.2±5min for nulliparous. There was a clinical average difference of 4.8min, with a maximum difference of 16.1min. These statistically significant difference account for an average increase of 13.7% in the operating time in multiparous versus nulliparous (p-value=0.0004, 95% CI=2.2-7.4min). Primary breast augmentation in parous women faces parenchymal and vascular histological breast tissue transformations which may not fully revert to the pre-pregnant state. These changes encountered during pocket dissection seem to have an impact on the operating time, cost-effectiveness and can therefore affect negatively surgical efficiency. Nevertheless, when surgical technique is based on sharp, precise dissection and proactive haemostasis, parity does not show to have an impact on the rates of complications, despite longer operation times.

General Anesthetic and Airway Management Practice for Obstetric Surgery in England: A Prospective, Multicenter Observational Study

(Anaesthesia. 2021;76:460–471) The use of general anesthesia (GA) in obstetrics is typically avoided due to concerns of increased risks, but is sometimes unavoidable. Accidental awareness during GA (AAGA) has been previously investigated by the Royal College of Anaesthetists and the Association of Anaesthetists in 2013. This study, the direct reporting of awareness in maternity patients (DREAMY) study aimed to determine the incidence, risk factors, and sequelae of AAGA. A secondary study within DREAMY sought to describe the provision of GA, including drugs and management techniques used in the United Kingdom.

Neuronal KCNQ2/3 channels are recruited to lipid raft microdomains by palmitoylation of BACE1.

β-Secretase 1 (β-site amyloid precursor protein [APP]-cleaving enzyme 1, BACE1) plays a crucial role in the amyloidogenesis of Alzheimer's disease (AD). BACE1 was also discovered to act like an auxiliary subunit to modulate neuronal KCNQ2/3 channels independently of its proteolytic function. BACE1 is palmitoylated at its carboxyl-terminal region, which brings BACE1 to ordered, cholesterol-rich membrane microdomains (lipid rafts). However, the physiological consequences of this specific localization of BACE1 remain elusive. Using spectral Förster resonance energy transfer (FRET), BACE1 and KCNQ2/3 channels were confirmed to form a signaling complex, a phenomenon that was relatively independent of the palmitoylation of BACE1. Nevertheless, palmitoylation of BACE1 was required for recruitment of KCNQ2/3 channels to lipid-raft domains. Two fluorescent probes, designated L10 and S15, were used to label lipid-raft and non-raft domains of the plasma membrane, respectively. Coexpressing BACE1 substantially elevated FRET between L10 and KCNQ2/3, whereas the BACE1-4C/A quadruple mutation failed to produce this effect. In contrast, BACE1 had no significant effect on FRET between S15 probes and KCNQ2/3 channels. A reduction of BACE1-dependent FRET between raft-targeting L10 probes and KCNQ2/3 channels by applying the cholesterol-extracting reagent methyl-β-cyclodextrin (MβCD), raft-disrupting general anesthetics, or pharmacological inhibitors of palmitoylation, all supported the hypothesis of the palmitoylation-dependent and raft-specific localization of KCNQ2/3 channels. Furthermore, mutating the four carboxyl-terminal cysteines (4C/A) of BACE1 abolished the BACE1-dependent increase of FRET between KCNQ2/3 and the lipid raft-specific protein caveolin 1. Taking these data collectively, we propose that the AD-related protein BACE1 underlies the localization of a neuronal potassium channel.