General Anesthetic Research Articles

A multi-site service evaluation of silver diamine fluoride use for children

Introduction The use of silver diamine fluoride (SDF) is relatively new to the UK. It is unknown how it is being used and for what indications in UK paediatric dental services.Aim To: 1) establish how SDF is being used across different paediatric dental settings in the UK; and 2) consider parental and patient views on the treatment experience and side effect of discolouration.Method A multi-site service evaluation was carried out across six paediatric dentistry units covering hospital and community services. Data were collected prospectively from 17/02/2020 to 02/03/2022. Simple descriptive statistics were used to analyse the data.Results Data were collected for 54 patients. The included patients had an age range of 2-13 years, with a mean of 4.9 years. The reason SDF was chosen was reported as: to avoid general anaesthetic (n = 25); to avoid extractions (n = 8); stabilisation (n = 25); acclimatisation (n = 24); and insufficient cooperation for other treatment (n = 17). In total, 42 cases had SDF applied to the primary dentition. This was in the anterior dentition for 18 patients and the posterior dentition for 15, with nine patients having SDF applied both anteriorly and posteriorly. The majority of children and parents were accepting of the technique and immediate aesthetic outcome.Conclusion In the services involved in this multi-site service evaluation, SDF is used for young patients in the primary dentition for the purpose of caries arrest. The technique was viewed positively by the majority of parents and children.

P29 The use of adjunct oral methotrexate as primary prevention for keloid scarring following syndactyly release surgery

Abstract A 12-month-old Asian female underwent syndactyly release surgery with advancement flap closure of the first web space of the right hand. The procedure was complicated by enlarging keloids over the surgical site and dactylitis, a rare complication with only a few previously reported cases [Muzaffar AR, Rafols F, Masson J et al. Keloid formation after syndactyly reconstruction: associated conditions, prevalence, and preliminary report of a treatment method. J Hand Surg Am 2004; 29: 201–8. https://doi.org/10.1016/j.jhsa.2003.10.017]. Initial treatment of the keloid scarring with intralesional triamcinolone under general anaesthetic was unsuccessful. Subsequently, we elected to surgically excise the keloids closing with a full-thickness skin graft from the groin, with adjunct oral methotrexate (0.4 mg kg–1 weekly) for 9 months post-surgery. The use of oral methotrexate for this indication is rarely reported: one series included two cases of successful keloid suppression with 4 years of follow-up [Muzaffar et al.] and another series of four patients with successful keloid suppression after surgery for syndactyly with dactylitis [Tolerton SK, Tonkin MA. Keloid formation after syndactyly release in patients with associated macrodactyly: management with methotrexate therapy. J Hand Surg Eur 2011; 36: 490–7]. Low-dose methotrexate exerts anti-inflammatory effects by stimulating adenosine A2 receptors and increasing adenosine release at sites of inflammation, such as surgical sites [Muzaffar et al.]. In our patient, methotrexate was well-tolerated, keloid recurrence and dactylitis were avoided, and range of movement and functioning of the digits was maintained. Keloid formation after syndactyly release poses a complex management challenge and we propose methotrexate should be considered as an adjunct to reduce recurrence risk.

Role of Minimal Dose of Norepinephrine in Prevention of Hypotension Induced by Subarachnoid Anesthesia in Elective Cesarean Section

Abstract Background Maternal hypotension is a common complication after spinal anesthesia for cesarean delivery. Spinal anesthesia techniques produce hypotension through blockade of sympathetic nerve fibers which control vascular smooth muscle tone. For elective cesarean section, regional anesthesia is preferred as a technique to general anesthesia because of maternal and fetal show a risk to morbidity and mortality. Spinal anesthesia for cesarean section allows the mother to be awake, minimizes or completely avoids the problem of maternal aspiration, and avoids neonatal drug depression from general anesthetics. Aim of the Work The aim of this study to assess the effectiveness of minimal dose of norepinephrine in preventing the episodes of hypotension that follow subarachnoid anesthesia in elective cesarean section. Patients and Methods The study was conducted on 60 randomly chosen patients full filling the inclusion criteria at Ain-Shams university hospitals after approval of medical committee. They were allocated in two groups of 30 patients each: Group (A) received the minimal dose of norepinephrine (25 nanogram/kg/h). Group (B) didn’t receive an infusion with vasopressor. Results The patients in the study group (A) had less events of hypotension 10% compared to 76% in group (B) and less Tachycardia in group (A) with only 3.3% compared to group (B) which were 70%. Although no statistical difference in all other parameters measured in this study. Conclusion Our study suggests that the use of norepinephrine as a vasopressor in the treatment of subarachnoid induced hypotension is safe and effective.

Simple steps towards improving safety in obstetric airway management: A quality improvement project.

Guidelines from the Obstetric Anaesthetists' Association and Difficult Airway Society state that 'a videolaryngoscope should be immediately available for all obstetric general anaesthetics'. To report the incidence of videolaryngoscopy use, and other airway management safety interventions, in an obstetric population before and after various quality improvement interventions. Prospective data collection was undertaken over 18 months, divided into three separate 6-month periods: June to November 2019; March to August 2021; January to June 2022. These periods relate to evaluation of specific quality improvement interventions. The project was carried out in a large tertiary referral obstetric unit. We identified 401 pregnant women (> 20 weeks' gestation) and postnatal women (up to 48 h post delivery) undergoing an obstetric surgical procedure under general anaesthesia. To standardise practice, an intubation checklist was introduced in December 2020 and multidisciplinary staff training in August 2021. Primary outcome measures were use of a Macintosh-style videolaryngoscope and tracheal intubation success. Secondary outcome measures were use of an intubation checklist; low flow nasal oxygen; and ramped patient positioning. Data from 334 tracheal intubations (83.3% of cases) were recorded. Videolaryngoscope use increased from 60% in 2019, to 88% in 2021, to 94% in 2022. Tracheal intubation was successful in all patients, with 94% first pass success overall and only 0.9% requiring three attempts. Use of secondary outcome measures also increased: low flow nasal oxygen from 48% in 2019 to 90% in 2022; ramped positioning from 95% in 2021 to 97% in 2022; and checklist use from 63% in 2021 to 92% in 2022. We describe the successful adoption of simple safety measures introduced into routine practice. These comprised videolaryngoscopy, ramped positioning and low flow nasal oxygen. Their introduction was supported by the implementation of an intubation checklist and multidisciplinary team training.

MANUAL VACUUM ASPIRATOR (MVA)- A SAFE AND EFFECTIVE ALTERNATIVE TO CONVENTIONAL CURETTAGE IN THE SURGICAL MANAGEMENT OF 1ST TRIMESTER MISCARRIAGES

Objective: To compare the efficacy of manual vacuum aspiration and conventional evacuation & curettage (ENC) for first-trimester miscarriage management. Materials and Methods: This quasi-experimental study was carried out at the Department of Gynecology and Obstetrics, Khyber Teaching Hospital, Peshawar, Pakistan from October 2022 to March 2023 including 150 patients with first trimester miscarriage dividing them into two groups (MVA and ENC) having equal number of patients. Efficacy in both groups was compared. Results: The mean age in the MVA group (group A) was 27.81±6.31years while in the ENC group (group B) it was 26.50±6.27 years. The mean gestational age in group A was 5.82±2.82 weeks while in group B it was 5.95±2.9 weeks. MVA was effective in 88% of participants while ENC was effective in 93.33% of participants (p-value, 261), which is not statistically significant. Conclusion: Surgical uterine evacuation utilizing MVA under local anesthetic is safe and successful, and it should be considered to minimize a lengthy hospital stay. MVA can be a viable alternative to surgical curettage like ENC. It is safe, cost-effective, and simple to conduct, eliminating general anesthetic, the requirement for theatre access, and an unnecessary hospital stay. Keywords: Manual Vacuum Aspiration, Evacuation, Curettage, miscarriage, efficacy.

A Rare Case of Long TNS following Caesarean Section under Spinal Anaesthesia

The first regional anaesthetic technique performed was spinal anaesthesia, and the first operation under spinal anaesthesia was in 1898 in Germany by August Bier. Spinal anaesthesia (SPA) is in common use worldwide for surgical procedures involving the lower abdomen, pelvis, perineal and lower extremities. It is beneficial for procedures below the umbilicus. Currently more than 50% global surgical patients undergo spinal anaesthesia every year. It is estimated that in USA 50 million individual were given spinal anaesthesia in 2022 and in India 60% of surgeries were performed under RA in 2021 as per a recent survey. Benefits of Spinal anaesthesia include prompt recovery, early return of normal functions, low chances of a blood clot following surgery and has less incidence of sickness, vomiting, when compared to a general anaesthetic for similar procedure. While acknowledging the benefits of SPA, Anaesthetists should be aware of and must inform clients of common side effects like acute back pain after spinal injection, that resolves with simple measures, Nausea, vomiting, headache and hypotension and Low-frequency hearing loss. One of the rare complications called Transient Neurologic Symptoms (TNS) with symptoms of, exclusive pain in buttocks, thighs, legs, few hours to ~ 1 day, lasting up to 10 days. After initial pain patient may notice numbness usually in left buttock area and weakness in gluteal muscles involved, that may prolong for 6 months to a year. The incidence India is quoted as 10-12 cases per lakh spinal anaesthesia procedures mainly caesarean sections. This article is of one such case the author is managing since a month. A 26-year-old lady primigravida, underwent caesarean section for the delivery 2 months ago. She was more concerned about the premature baby’s feeding challenges, but coincidentally brought to author’s notice. She has been put on a few o lower limb and abdominal muscle strengthening exercises and supplemented Tablet Neurobion (vit B12) forte one tablet a day. As of 22 /08/23 she has improved muscle power (20%) able to sit up with the support of upper and Numbness has also improved a bit. Material & Methods: One rare case of TNS, clinical diagnosis, management, Physiotherapy, Literature review and case report studies.

ThTP3.11 Abscess Incision and Drainage Under Local Anaesthetic: Greener, Faster, Cheaper

Abstract Introduction It is standard practise for incision and drainage (I+D) of abscesses in our general surgery department to be performed under general anaesthetic (GA), despite evidence that local anaesthetic (LA) drainage is safe and effective. Aims To evaluate the acceptability and environmental benefits of LA abscess I+D. Methods Data were collected for abscesses assessed from January-July 2022. Abscesses that were >5cm, perianal/perineal, on multiple sites, or drained during another procedure were deemed unsuitable for LA. Questionnaires to evaluate patient opinions on sustainability were distributed to 26 patients requiring I+D from November-December 22. Carbon footprints were calculated using published carbon footprint estimates for patient travel and healthcare activity. Results 130 of the 162 patients seen with abscesses underwent I+D, with 119 done under GA. Of those who had GA I+D, 71 were possibly suitable for LA. Of these 71 patients, 66 were done the following day, requiring admission or the patient to go home and return. The estimated additional carbon footprint of performing these procedures under GA was 1,806kgCO2e. 84% of patients surveyed thought it was ‘important’ or ‘very important’ that their procedure was cost effective, and 57% thought it was ‘important’ or ‘very important’ that their procedure was good for the environment. Conclusion Performing suitable abscesses under LA could save 3,096kgCO2e per year: equivalent to driving 19,000km. It would also save money, emergency list space and be more convenient for patients. It is important to many of our patients that their treatments are sustainable.

ThTP5.5 The Emergency laparotomy – “scans, tubes and scalpels”. A report from the UK’s first collaborative National Emergency Laparotomy Audit (NELA) training meeting

Abstract Background & Aims Time-critical emergency laparotomies are routinely performed nationally. These complex patients often require multi-disciplinary discussion of pre-operative imaging and intra-operative and post-operative status. NELA is designed to improve patient outcomes, encouraging regular audit and quality improvement. We report the outcomes of the UK’s first collaborative NELA training meeting from a Major Trauma Centre in London This unique meeting aimed to: Methods Three complex laparotomy patients were discussed using case-based discussions involving General Surgery, Anaesthetics and Radiology and involving imaging, intra-operative photographs and anaesthetic information. Pre- and post-meeting participant questionnaires were disseminated for comparative analysis. Results 39 attended the evening (50% radiologists, 25% surgeons, 25% anaesthetists); two thirds’ trainees. 100% attendee satisfaction rate was recorded. 46% of attendees were not aware of NELA prior to the meeting. Post meeting, 95% of attendees were confident in their understanding of the NELA process. There was a 25% increase in the knowledge of NELA reporting outcome measures (to 95%) and 90% correctly named the specialities involved. 96% of attendees reported interest in attending a subsequent meeting. Conclusion Complex emergency patients require expert cross-specialty input to drive improvements in patient outcomes. We believe this to be the first multidisciplinary NELA education meeting. Improvement in attendee understanding demonstrates the success of shared learning via case-based discussion to improve patient care. We aim to continue local meetings with aspirations to future national events.

ThTP8.10 Creating a Team Culture of Building a reliable NELA Database in a District General Hospital

Abstract Introduction In St Helier Hospital, Surrey, we run a busy Emergency General Surgery Service, performing almost 200 laparotomies annually. It is remarkable that in our Department every laparotomy case is consultant-led and that the percentage of HDU admission of high perioperative risk cases reaches 100%, leading to survival rates that are above the UK average. However, the NELA database has not been updated consistently with cases missing and others entered erroneously. As a result, the NELA database does not reliably reflect the quality of care we provide to our patients and undermines the Department’s CQC metrics. Methods We established a multidisciplinary QI Project involving the Departments of General Surgery, Anaesthetics and Intensive Care to create a team culture of commitment to NELA collection data. Interventions Results Conclusion Simple measures as well as raising awareness among the implicated professionals has led to great improvement in adherence to updating NELA database.

Remimazolam's Effects on Postoperative Nausea and Vomiting Are Similar to Those of Propofol after Laparoscopic Gynecological Surgery: A Randomized Controlled Trial.

(1) Background: Remimazolam is a novel benzodiazepine that prevents postoperative nausea and vomiting (PONV), is more effective than volatile anesthetics, and was recently approved for use in Japan. (2) Methods: This prospective, double-blind, randomized controlled trial study aimed to compare the efficacy of remimazolam and propofol as general anesthetics in terms of the incidence of PONV after laparoscopic gynecological surgery (UMIN000046237). High-risk female patients who underwent general anesthesia with either remimazolam or propofol for the maintenance of anesthesia were enrolled. The primary outcome was the incidence of PONV in the two groups (i.e., REM versus PROP) 2 h and 24 h after surgery. The incidence of vomiting without nausea, rescue antiemetic use, and the severity of nausea were also evaluated. (3) Results: No significant differences in PONV were identified between the REM and PROP groups at 2 h or 24 h. Furthermore, no differences were observed in any of the measured parameters, and no adverse events were reported. (4) Conclusions: The results of the present study suggest that remimazolam may be as effective as propofol in preventing PONV; however, further investigation is necessary to identify possible differences between these two agents.

A survey of surgical patients’ perspectives and preferences towards general anesthesia techniques and shared-decision making

BackgroundThe decision about which type of general anesthetic to administer is typically made by the clinical team without patient engagement. This study examined patients’ preferences, experiences, attitudes, beliefs, perceptions, and perceived social norms about anesthesia and about engaging in the decision regarding general anesthetic choice with their clinician.MethodsWe conducted a survey in the United States, sent to a panel of surgical patients through Qualtrics (Qualtrics, Provo, UT) from March 2022 through May 2022. Questions were developed based on the Theory of Planned Behavior and validated measures were used when available. A patient partner who had experienced both intravenous and inhaled anesthesia contributed to the development and refinement of the questions.ResultsA total of 806 patients who received general anesthesia for an elective procedure in the last five years completed the survey. 43% of respondents preferred a patient-led decision making role and 28% preferred to share decision making with their clinical team, yet only 7.8% reported being engaged in full shared decision making about the anesthesia they received. Intraoperative awareness, pain, nausea, vomiting and quickly returning to work and usual household activities were important to respondents. Waking up in the middle of surgery was the most commonly reported concern, despite this experience being reported only 8% of the time. Most patients (65%) who searched for information about general anesthesia noted that it took a lot of effort to find the information, and 53% agreed to feeling frustrated during the search.ConclusionsMost patients prefer a patient-led or shared decision making process when it comes to their anesthetic care and want to be engaged in the decision. However, only a small percentage of patients reported being fully engaged in the decision. Further studies should inform future shared decision-making tools, informed consent materials, educational materials and framing of anesthetic choices for patients so that they are able to make a choice regarding the anesthetic they receive.

Astrocytes Are Involved in the Effects of Ketamine on Synaptic Transmission in Rat Primary Somatosensory Cortex.

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used as a general anaesthetic. However, the mechanisms of analgesic/anaesthetic effects induced by ketamine are only partially understood. Previously, studies have demonstrated that various general anaesthetics affect the primary somatosensory cortex (S1), a potential target of general anaesthetics in the central nervous system. However, it is unknown if astrocyte activities affect ketamine's effects on information transmission in S1 pyramidal neurons. The whole-cell patch-clamp technique was employed to study the role of astrocytes in ketamine-induced anaesthetic actions. The whole-cell patch-clamp method was used to record the spontaneous postsynaptic currents (SPSCs) of rat S1 pyramidal neurons. We used the glia-selective inhibitor of the aconitase enzyme fluorocitrate (FC), to test if astrocyte activities alter the effects of ketamine on S1 pyramidal neurons. Ketamine lowered the SPSCs of rat S1 pyramidal neurons in a concentration-dependent manner at clinically relevant doses. The concentration-effect curve revealed that ketamine had an EC50 value of 462.1 M for suppressing SPSCs. In rat S1 pyramidal neurons, the glia-selective metabolic inhibitor fluorocitrate (FC), which inhibits the aconitase enzyme, lowered the amplitude and frequency of SPSCs. The inhibitory impact of ketamine on the amplitude and frequency of SPSCs was significantly amplified in the presence of FC. Astrocytes impact the effects of ketamine on pre- and postsynaptic components and play a role in synaptic transmission.

Effects of propofol and sevoflurane on social and anxiety-related behaviours in sleep-deprived rats

BackgroundSleep disorders can profoundly affect neurological function. We investigated changes in social and anxiety-related brain functional connectivity induced by sleep deprivation, and the potential therapeutic effects of the general anaesthetics propofol and sevoflurane in rats. MethodsTwelve-week-old male Sprague–Dawley rats were subjected to sleep deprivation for 20 h per day (from 14:00 to 10:00 the next day) for 4 consecutive weeks. They were free from sleep deprivation for the remaining 4 h during which they received propofol (40 mg kg–1 i.p.) or sevoflurane (2% for 2 h) per day or no treatment. These cohorts were instrumented for EEG/EMG recordings on days 2, 14, and 28. Different cohorts were used for open field and three-chambered social behavioural tests, functional MRI, nuclear magnetic resonance spectroscopy, and positron emission tomography imaging 48 h after 4 weeks of sleep deprivation. ResultsPropofol protected against sleep deprivation-induced anxiety behaviours with more time (44.7 [8.9] s vs 24.2 [4.1] s for the sleep-deprivation controls; P<0.001) spent in the central area of the open field test and improved social preference index by 30% (all P<0.01). Compared with the sleep-deprived rats, propofol treatment enhanced overall functional connectivity by 74% (P<0.05) and overall glucose metabolism by 30% (P<0.01), and improved glutamate kinetics by 20% (P<0.05). In contrast, these effects were not found after sevoflurane treatment. ConclusionsUnlike sevoflurane, propofol reduced sleep deprivation-induced social and anxiety-related behaviours. Propofol might be superior to sevoflurane for patients with sleep disorders who receive anaesthesia, which should be studied in clinical studies.

The safety and efficacy between remimazolam and propofol in intravenous anesthesia of endoscopy operation: a systematic review and meta-analysis.

Propofol is the most widely used intravenous anesthetic in endoscopic surgery, but is associated with several adverse reactions. Public research has shown that remimazolam, a safe general anesthetic, is increasingly being used as a substitute for propofol in clinical operations. Our meta-analysis aimed to analyze whether the adverse reaction rate of remimazolam in endoscopic surgery is acceptable and whether the surgical success rate is not lower than that of propofol. This meta-analysis examined the adverse events and efficacy of remimazolam vs. propofol during endoscopic surgery. MEDLINE, Embase, ClinicalTrials.gov, and Google Scholar were comprehensively searched. Seven studies comparing remimazolam and propofol were included in our meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane manual were used to assess the quality of the results published in all included studies to ensure that our meta-analysis results are reliable and worthwhile. Compared to propofol, the use of remimazolam reduced postoperative injection pain [relative risk (RR)=0.06, 95% confidence interval (CI): 0.03-0.12, P <0.00001], postoperative hypotension (RR=0.45, 95% CI: 0.28-0.73, P =0.001), and postoperative respiratory depression (RR=0.20, 95% CI: 0.08-0.47, P =0.0002); however, it also slightly reduced the success rate of the operation [risk difference (RD)=-0.02, 95% CI: -0.04 to -0.01, P =0.0007]. There were no significant differences in the occurrence of bradycardia symptoms after the operation (RD=-0.01, 95% CI: -0.03 to 0.01, P =0.35), recovery time after the operation [standardized mean difference (SMD)=0.68, 95% CI: -0.43 to 1.80, P =0.23] or discharge time (SMD=0.17, 95% CI: -0.58 to 0.23, P =0.41). We also performed a subgroup analysis of each corresponding outcome. Our analysis showed that remimazolam may be a safer shock option than propofol for endoscopic surgery. However, further research is required to determine their utility.

Thiopental sodium attenuates hypoxia/reoxygenation-induced injury in osteoblasts by modulating AKT signaling.

Thiopental sodium (TPTS) is a barbiturate general anesthetic, while its effects on hypoxia/reoxygenation (H/R)-induced injury are still unclear. This study aimed to investigate whether TPTS exerts protective effects against the H/R-induced osteoblast cell injury and explore the underlying mechanisms. Osteoblast cell injury model was induced by the H/R condition, which was treated with or without TPTS. Cell viability and lactate dehydrogenase (LDH) release were determined by the corresponding commercial kits. The levels of oxidative stress were determined in the experimental groups. Cell apoptosis and Caspase-3 activities were determined by propidium iodide staining and substrate-based assay, respectively. Western blotting and qRT-PCR were performed to measure the mRNA and protein levels, respectively. Treatment with TPTS was able to increase cell viability and reduce LDH release in H/R-induced osteoblasts. Additionally, TPTS regulated oxidative stress in H/R-induced osteoblasts by suppressing malondialdehyde (MDA) and reactive oxygen species (ROS) as well as boosting superoxide dismutase (SOD). TPTS was able to suppress cell apoptosis by suppressing Caspase-3 activity and cleavage. TPTS exerted protective effects against cell injury and apoptosis induced by the H/R conditions, which were associated with its regulation of Akt signaling. Moreover, TPTS induced osteoblast differentiation under the H/R condition. In summary, TPTS attenuates H/R-induced injury in osteoblasts by regulating AKT signaling.

Propofol elicits apoptosis and attenuates cell growth in esophageal cancer cell lines.

Propofol is a pharmaceutical agent commonly used as an intravenous anesthetic in surgical treatments and a sedative in intensive care. However, it is largely unknown how exposure to propofol affects the proliferation, invasion, and apoptosis of neoplastic cells in esophageal cancer. In this study, we sought to elucidate the impact of propofol exposure on the growth properties of human esophageal cancer cell lines in vitro. We treated two human esophageal cancer cell lines, KYSE30 and KYSE960, with up to 10 µg/mL of propofol for 12-36 h. The treated cells were then analyzed by cell proliferation assay, Matrigel invasion assay, quantification of caspase-3/7 and -9 activities, and cell staining with Annexin V and 7-aminoactinomycin D to detect early apoptosis and cell death, respectively, via flow cytometry. We found that 3-5 µg/mL propofol reduced the growth and Matrigel invasion of both cell lines in a dose-dependent manner. Executioner caspase-3/7, but not caspase-9 involved in intrinsic apoptosis pathway, was activated by cell exposure to 3-5 µg/mL propofol. In addition, 3-5 µg/mL propofol augmented early apoptosis in both cell lines and increased cell death in the KYSE30 cell line. In summary, exposure to propofol, at concentrations up to 5 µg/mL, led to the reduction of cell growth and Matrigel invasion, as well as the augmentation of apoptosis in esophageal cancer cell lines. These data will help define a methodology to safely utilize propofol, a common general anesthetic and sedative, with esophageal cancer patients.

The States of Different 5-HT Receptors Located in the Dorsal Raphe Nucleus Are Crucial for Regulating the Awakening During General Anesthesia.

General anesthesia is widely used in various clinical practices due to its ability to cause loss of consciousness. However, the exact mechanism of anesthesia-induced unconsciousness remains unclear. It is generally thought that arousal-related brain nuclei are involved. 5-Hydroxytryptamine (5-HT) is closely associated with sleep arousal. Here, we explore the role of the 5-HT system in anesthetic awakening through pharmacological interventions and optogenetic techniques. Our data showed that exogenous administration of 5-hydroxytryptophan (5-HTP) and optogenetic activation of 5-HT neurons in the dorsal raphe nucleus (DR) could significantly shorten the emergence time of sevoflurane anesthesia in mice, suggesting that regulation of the 5-HT system using both endogenous and exogenous approaches could mediate delayed emergence. In addition, we first discovered that the different 5-HT receptors located in the DR, known as 5-HT autoreceptors, are essential for the regulation of general anesthetic awakening, with 5-HT1A and 5-HT2A/C receptors playing a regulatory role. These results can provide a reliable theoretical basis as well as potential targets for clinical intervention to prevent delayed emergence and some postoperative risks.

Cellular consequences triggered by ketamine on exposure to human glioblastoma epithelial (LN-229) cells.

Ketamine is generally a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that interrelates with various other receptors, contributing to a wide range of actions. They are mainly approved as a general anesthetic, but a low dose of ketamine is applied for pain management, depression, and as analgesics. However, there is a significant concern regarding the long-term usage as antidepressants and as an abused drug. The study mainly aims to exhibit the possible long-term side effects of ketamine as an antidepressant and in recreational users. The study explores the in vitro cytotoxicity revealed on LN-229 cells in a dose-dependent manner. According to the cell viability assays, there is a dose-dependent response toward ketamine. Morphological and nuclear integrity was changed on exposure and assessed using Giemsa, Rhodamine phalloidin, 4',6-diamidino-2-phenylindole (DAPI), and Acridine orange staining. The apoptotic cell death marked by nuclear condensation, Lactate dehydrogenase leakage, pro-inflammatory cytokine (interleukin [IL]-β) release, and inhibition of cell migration was observed. The study highlights the importance of nonanesthetic usage of ketamine, which can lead to severe adverse side effects on long-term exposure rather than a single exposure as an anesthetic agent.

Anesthetic Considerations in Patients with Mitochondrial Disorders

Introduction: Mitochondrial Disorders (1/4,000 patients) are rare and caused by dysfunctional mitochondria. Anesthetic consideration in patients with Mitochondrial Disorders involves careful preoperative and perioperative observations. Objective: To provide a brief insight into how general anesthetics interfere with mitochondrial energy formation pathways and help form precautions for anesthesiologists when managing patients with Mitochondrial Disorder. Review: Mitochondrial Disorder patients would experience various health problems, such as damaged cardiac functions, neurology systems, and musculoskeletal functions due to energy production disruptions by dysfunctional mitochondrial processes. Moreover, patients with Mitochondrial Disorders exhibit hyperreactivity to volatile anesthetics. Summary: No anesthetic strategies are found to be safe in patients with Mitochondrial Disorder yet. Therefore, anesthesiologists should remain alert when monitoring fluid choices and managing patient temperature with Mitochondrial Disorders.

Propofol Inhibits Glioma Stem Cell Growth and Migration and Their Interaction with Microglia via BDNF-AS and Extracellular Vesicles.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. GBM contains a small subpopulation of glioma stem cells (GSCs) that are implicated in treatment resistance, tumor infiltration, and recurrence, and are thereby considered important therapeutic targets. Recent clinical studies have suggested that the choice of general anesthetic (GA), particularly propofol, during tumor resection, affects subsequent tumor response to treatments and patient prognosis. In this study, we investigated the molecular mechanisms underlying propofol's anti-tumor effects on GSCs and their interaction with microglia cells. Propofol exerted a dose-dependent inhibitory effect on the self-renewal, expression of mesenchymal markers, and migration of GSCs and sensitized them to both temozolomide (TMZ) and radiation. At higher concentrations, propofol induced a large degree of cell death, as demonstrated using microfluid chip technology. Propofol increased the expression of the lncRNA BDNF-AS, which acts as a tumor suppressor in GBM, and silencing of this lncRNA partially abrogated propofol's effects. Propofol also inhibited the pro-tumorigenic GSC-microglia crosstalk via extracellular vesicles (EVs) and delivery of BDNF-AS. In conclusion, propofol exerted anti-tumor effects on GSCs, sensitized these cells to radiation and TMZ, and inhibited their pro-tumorigenic interactions with microglia via transfer of BDNF-AS by EVs.