Patient Satisfaction With, and Outcomes of, Ultrasound-Guided Regional Anesthesia at a Referral Hospital in Tanzania: A Cross-Sectional Study.

BACKGROUND: Regional anesthesia techniques are increasingly used in high-income countries (HICs) for both surgical anesthesia and postoperative analgesia. However, regional anesthesia has not been utilized to the same degree in low- to middle-income countries (LMICs) due to a lack of resources and trained personnel. This study evaluates patient satisfaction with, and outcomes of, ultrasound-guided regional anesthesia for extremity surgery at Kilimanjaro Christian Medical Center (KCMC) in the Northeastern zone of Tanzania. METHODS: Study patients were ≥18 years of age; American Society of Anesthesiologists (ASA) physical status I, II, or III; and underwent extremity surgery under peripheral nerve block with ultrasound guidance at KCMC. After placement, blocks were assessed for effectiveness intraoperatively, as demonstrated by the need for supplemental analgesic or sedative medication or conversion to a general anesthetic. Postoperatively, patients were assessed for satisfaction with their nerve block and pain at 12 and 24 hours. Adverse events related to regional anesthesia were assessed immediately, 45 minutes after block placement, and at 12 and 24 hours postoperatively. The primary outcome was patient satisfaction at 12 hours. Secondary outcomes were block success rate and analgesia at 12 and 24 hours postoperatively. RESULTS: A convenience sample of 170 patients was included in the study, of whom 156 (95% confidence interval [CI], 87-95) were either satisfied or very satisfied with their block. Block placement was highly successful with only 8 of 170 participants (95% CI, 2.4-8.3), requiring conversion to a general anesthetic. Analgesia continued in the postoperative period, with 164 of 170 (95% CI, 93-98) patients and 145 of 170 (95% CI, 80-90) patients reporting acceptable analgesia at 12 and 24 hours, respectively. No major adverse events, such as local anesthetic toxicity, infection, bleeding, nerve injury, or pneumothorax, were observed. CONCLUSIONS: Our study found that ultrasound-guided regional anesthesia in a resource-constrained setting was effective for extremity surgery and resulted in high patient satisfaction. No complications occurred. The use of ultrasound-guided regional anesthesia shows promise for the safe and effective care of patients undergoing extremity surgery in LMICs.

The Modulation by Anesthetics and Analgesics of Respiratory Rhythm in the Nervous System.

Rhythmic eupneic breathing in mammals depends on the coordinated activities of the neural system that sends cranial and spinal motor outputs to respiratory muscles. These outputs modulate lung ventilation and adjust respiratory airflow, which depends on the upper airway patency and ventilatory musculature. Anesthetics are widely used in clinical practice worldwide. In addition to clinically necessary pharmacological effects, respiratory depression is a critical side effect induced by most general anesthetics. Therefore, understanding how general anesthetics modulate the respiratory system is important for the development of safer general anesthetics. Currently used volatile anesthetics and most intravenous anesthetics induce inhibitory effects on respiratory outputs. Various general anesthetics produce differential effects on respiratory characteristics, including the respiratory rate, tidal volume, airway resistance, and ventilatory response. At the cellular and molecular levels, the mechanisms underlying anesthetic-induced breathing depression mainly include modulation of synaptic transmission of ligand-gated ionotropic receptors (e.g., γ-aminobutyric acid, N-methyl-D-aspartate, and nicotinic acetylcholine receptors) and ion channels (e.g., voltage-gated sodium, calcium, and potassium channels, two-pore domain potassium channels, and sodium leak channels), which affect neuronal firing in brainstem respiratory and peripheral chemoreceptor areas. The present review comprehensively summarizes the modulation of the respiratory system by clinically used general anesthetics, including the effects at the molecular, cellular, anatomic, and behavioral levels. Specifically, analgesics, such as opioids, which cause respiratory depression and the "opioid crisis", are discussed. Finally, underlying strategies of respiratory stimulation that target general anesthetics and/or analgesics are summarized.

Ultrasound-guided, continuous erector spinae plane (ESP) block in minimally invasive thoracic surgery-comparing programmed intermittent bolus (PIB) vs continuous infusion on quality of recovery and postoperative respiratory function: a double-blinded randomised controlled trial.

BACKGROUND: Minimally invasive thoracic surgery (MITS) has been shown to reduce postoperative pain and contribute to better postoperative quality of life as compared to open thoracic surgery (Bendixen et al., Lancet Oncol 17:836-44, 2016). However, it still causes significant post-operative pain. Regional anaesthesia techniques including fascial plane blocks such as the erector spinae plane block (ESP) have been shown to contribute to post-operative pain control after MITS (Finnerty et al., Br J Anaesth 125:802-10, 2020). Case reports relating to ESP catheters have described improved quality of pain relief using programmed intermittent boluses (PIB) instead of continuous infusion (Bendixen et al., Lancet Oncol 17:836-44, 2016). It is suggested that larger, repeated bolus dose may provide superior pain relief, possibly because of improved spread of the local anaesthetic medications (Ilfeld and Gabriel, Reg Anesth Pain Med 44:285-86, 2019). Evidence for improved spread of local anaesthetic may be found in one study which demonstrated that PIB increased the spread of local anaesthetic medication compared to continuous infusions for continuous paravertebral blocks, which are another type of regional anaesthesia technique for the chest wall (Hida et al., Reg Anesth Pain Med 44:326-32, 2019). Similarly, regarding labour epidural analgesia, the weight of evidence is in favour of PIB providing better pain relief compared with continuous infusion (Onuoha, Anesthesiol Clin 35:1-14, 2017). Since fascial plane blocks, such as ESP, rely on the spread of local anaesthetic medication between muscle layers of the chest wall, intermittent boluses may be particularly useful for this group of blocks. However, until recently, pumps capable of providing automated boluses in addition to patient-controlled boluses were not widely available. To best of our knowledge, there are no randomised controlled trials comparing continuous infusion versus intermittent bolus strategies for erector spinae plane block for MITS in terms of patient centred outcomes such as quality of recovery. METHODS: This trial will be a prospective, double-blinded, randomised controlled superiority trial. A total of 60 eligible patients will be randomly assigned to receive an intermittent bolus regime of local anaesthetic vs a continuous infusion of local anaesthetic. The medication will be delivered via an ultrasound-guided erector spinae plane block catheter which will be inserted by an anaesthesiologist while the patient is under general anaesthetic before their MITS surgery begins. The primary outcome being measured is the Quality of Recovery (QoR-15) score between the two groups 24 h after surgery. Secondary outcomes include respiratory testing of maximal inspiratory volume measured with a calibrated incentive spirometer, area under the curve for Verbal Rating Score for pain at rest and on deep inspiration versus time over 48 h, total opioid consumption over 48 h, QoR-15 score at 48 h and time to first mobilisation. DISCUSSION: Despite surgical advancements in thoracic surgery, severe acute post-operative pain following MITS is still prevalent. This study will provide new knowledge and possible recommendations about the efficacy of programmed intermittent bolus regimen of local anaesthetic vs a continuous infusion of local anaesthetic via an ultrasound-guided erector spinae plane catheter for patients undergoing MITS. TRIAL REGISTRATION: This trial was pre-registered on ClinicalTrials.gov Identifier: NCT05181371 . Registered on 6 January 2022. All item from the World Health Organization Trial Registration Data set have been included.

Re-intervention and patient satisfaction rates following office radiofrequency endometrial ablation: a comparative retrospective study of 408 cases.

This retrospective study assessed the efficacy and long-term satisfaction of radiofrequency endometrial ablation outside the context of clinical trials in 408 women, and compared the outcome between office-setting (211, 52%) and day-case procedures under general anaesthetics (197, 48%). The Kaplan Meir time-to-event analysis showed that the cumulative number of women undergoing surgical re-intervention was 32 with a probability of 9.4% (95% CI: 6.3 - 12.5%) at 2-years, and 45 with a probability of 14.5% (95% CI: 10.3 - 18.2%) at 5-years. There was no statistically significant difference in the re-intervention rate between office and day-case groups (HR = 0.7, 95% CI: 0.68 - 3.1, p = .3). The satisfaction rate, measured by Visual Analogue Scale, was not statistically different (p = .5) between office (109; 80.7%) and day-case (96; 82.8%) groups. This study showed lower surgical re-intervention rate than previously reported in observational studies, and high rates of long-term women satisfaction. The outcomes were similar in office and day-case settings.Impact statementWhat is already known on this subject? Previous studies have shown the safety and effectiveness of radiofrequency endometrial ablation for treating heavy periods. However, studies investigating it, outside clinical trials, either included a small sample size, a short-term follow-up, poor reporting so that it is impossible to judge whether some women underwent re-intervention in another centre, failed to discriminate in analysis between second-generation techniques, or assessed only short-term satisfaction.What do the results of this study add? This is the largest series reported from a single centre and the first study reporting long-term satisfaction in women, outside clinical trials. Surgical re-intervention was used as the primary outcome measure which is an objective measure rather than the change in the monthly flow which is rather subjective. More importantly, the study records the similarity, in the outcome and women's satisfaction rate, between office and day-case procedures under general anaesthetics.What are the implications of these findings for clinical practice and/or further research? Endometrial ablation service is widely implemented in office-setting in the UK. We hope the result of this study encourages implementation on a larger scale in office across centres in the world with its multiple advantages both to women and service alike.

Prevalence of postoperative delirium with different combinations of intraoperative general anesthetic agents in patients undergoing cardiac surgery: A retrospective propensity-score-matched study.

ABSTRACT: Postoperative delirium (PD) remains an issue in cardiac surgery despite the constant efforts to reduce its incidence. In this retrospective study, the incidence of PD was evaluated in patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) according to different primary anesthetic agents: sevoflurane and dexmedetomidine- versus propofol-based anesthesia.A total of 534 patients who underwent heart-valve surgery or coronary artery bypass graft surgery with CPB between January 2012 and August 2017 were divided into 2 groups according to the main anesthetic agent: sevoflurane with dexmedetomidine (sevo-dex group, n = 340) and propofol (propofol group, n = 194). The incidence of PD was evaluated as the primary outcome. Patient-, surgery-, and anesthesia-related factors and postoperative complications were investigated as secondary outcomes. To reduce the risk of confounding effects between the 2 groups, 194 patients were selected from the sevo-dex group after propensity-score matching.After propensity-score matching, the incidence of PD was not significantly different between the sevo-dex (6.2%) and propofol (10.8%) groups (P = .136). In comparisons of the incidence of each type of PD, only hyperactive PD occurred significantly less frequently in the sevo-dex group (P = .021). Older age, lower preoperative albumin levels, and emergency surgery were significant risk factors for PD.The overall incidence of PD after cardiac surgery with CPB did not differ between patients receiving sevoflurane and dexmedetomidine-based versus propofol-based anesthesia. Only hyperactive PD occurred less frequently in patients receiving sevoflurane and dexmedetomidine-based anesthesia.

Anesthetics and plants: no pain, no brain, and therefore no consciousness.

Plants have a rich variety of interactions with their environment, including adaptive responses mediated by electrical signaling. This has prompted claims that information processing in plants is similar to that in animals and, hence, that plants are conscious, intelligent organisms. In several recent reports, the facts that general anesthetics cause plants to lose their sensory responses and behaviors have been taken as support for such beliefs. These lipophilic substances, however, alter multiple molecular, cellular, and systemic functions in almost every organism. In humans and other animals with complex brains, they eliminate the experience of pain and disrupt consciousness. The question therefore arises: do plants feel pain and have consciousness? In this review, we discuss what can be learned from the effects of anesthetics in plants. For this, we describe the mechanisms and structural prerequisites for pain sensations in animals and show that plants lack the neural anatomy and all behaviors that would indicate pain. By explaining the ubiquitous and diverse effects of anesthetics, we discuss whether these substances provide any empirical or logical evidence for "plant consciousness" and whether it makes sense to study the effects of anesthetics on plants for this purpose. In both cases, the answer is a resounding no.

Comparison of Sevoflurane and Propofol on the Incidence of Postoperative Pain and Quality of Life in Patients Undergoing Total Knee Arthroplasty With Chronic Pain Before Surgery.

BACKGROUND: Propofol and sevoflurane as frequently used general anesthetics can affect postoperative pain. Our study explored whether the incidence of postoperative pain differed among patients with chronic pain undergoing total knee arthroplasty (TKA) anesthetized with sevoflurane or propofol. METHODS: Patients were randomly assigned to groups receiving either sevoflurane (Group S, n = 50) or propofol (Group P, n = 47) for anesthesia maintenance during TKA. The incidences of postoperative pain and quality of life (QoL) were measured using the EuroQol 5-Dimension (EQ-5D) scale at 1, 3, and 7 days post-operation (DPO), and 1 and 3 months post-operation (MPO). RESULTS: At 3 DPO, fewer patients reported moderate pain (P = 0.001) and more patients reported no pain (P = 0.003) in Group S than that in Group P. At 3 MPO, more patients reported no pain (P = 0.04) and fewer patients reported moderate pain (P = 0.04) in Group S than in Group P. No significant differences were found in the incidence of postoperative pain between the 2 groups of patients at the other time points. The EQ-5D scores were higher in Group S than in Group P (P = 0.022), and the difference was 0.15 at most, which was not optimal. The EQ-5D clinical results might be not very significant. CONCLUSIONS: Sevoflurane anesthesia may have potential advantages in reducing postoperative pain in patients undergoing TKA with a preoperative VAS score > 4.

Manejo anestésico de hipertensión intracraneal y embarazo. Informe de un caso / Anaesthetic management of intracranial hypertension and pregnancy. A case report

La hidrocefalia es una distensión activa del sistema ventricular del cerebro. Las mejores tasas de supervivencia de los pacientes con enfermedad neuroquirúrgica se acompañan de un mayor número de procedimientos no neuroquirúrgicos en pacientes que tienen dispositivos neuroquirúrgicos terapéuticos. No está clara la verdadera incidencia del embarazo en pacientes con hidrocefalia obstructiva controlada con derivación ventriculoperitoneal (DVP). Presentamos un caso de una mujer embarazada de 34 años con una DVP para hidrocefalia obstructiva. Debido a la obstrucción de la DVP secundaria al volumen del útero, ella presentó varios episodios de deterioro neurológico durante el embarazo. Se planificaron una cesárea electiva y una revisión de la DVP para el mismo tiempo operatorio. Este caso inusual representa un desafío al que el anestesiólogo debe enfrentarse para proporcionar el mejor manejo simultáneo del delicado bienestar de la madre, su cerebro, y el feto

Hydrocephalus is an active distension of the ventricular system of the brain. The improved survival rates of patients with neurosurgical pathology is accompanied by a greater number of non-neurosurgical procedures in patients who have therapeutic neurosurgical devices. The real incidence of pregnancy in patients with obstructive hydrocephalus controlled with ventriculoperitoneal shunt (VPS) is unclear. We present a case of a pregnant 34-year-old female with a VPS for obstructive hydrocephalus. Due to VPS obstruction secondary to uterus volume, she presented several episodes of neurological impairment during pregnancy. An elective caesarean section (C-section) and VPS review were planned for the same operative time. This rare case reflects the challenge that the anaesthesiologist has to face in order to provide the best and simultaneous management of the wellbeing of the mother, the mother's brain and the foetus

General Anesthetic-Induced Neurotoxicity in the Immature Brain: Reevaluating the Confounding Factors in the Preclinical Studies.

General anesthetic (GA) is used clinically to millions of young children each year to facilitate surgical procedures, relieve perioperative stress, and provide analgesia and amnesia. During recent years, there is a growing concern regarding a causal association between early life GA exposure and subsequently long-term neurocognitive abnormalities. To address the increasing concern, mounting preclinical studies and clinical trials have been undergoing. Until now, nearly all of the preclinical findings show that neonatal exposure to GA causally leads to acute neural cell injury and delayed cognitive impairment. Unexpectedly, several influential clinical findings suggest that early life GA exposure, especially brief and single exposure, does not cause adverse neurodevelopmental outcome, which is not fully in line with the experimental findings and data from several previous cohort trials. As the clinical data have been critically discussed in previous reviews, in the present review, we try to analyze the potential factors of the experimental studies that may overestimate the adverse effect of GA on the developing brain. Meanwhile, we briefly summarized the advance in experimental research. Generally, our purpose is to provide some useful suggestions for forthcoming preclinical studies and strengthen the powerfulness of preclinical data.

Anesthetic Management During Electroconvulsive Therapy in Children: A Systematic Review of the Available Literature.

Electroconvulsive therapy (ECT) is indicated in a myriad of pediatric psychiatric conditions in children, and its use is increasing. Literature on the clinical features salient to anesthetic care is lacking. The objective of this systematic review is to describe the available literature on the anesthetic considerations of pediatric ECT. Original publications were screened for inclusion criteria: (1) manuscript written in English; (2) persons under 18 years of age; and (3) use of ECT. Data tabulation included demographic information, details of anesthetic management and ECT procedure, and adverse events. The mean age was 15 years, 90% were 12-17 years of age, and no cases involving children <6 years of age were identified. The psychiatric diagnoses most commonly represented were major depressive disorder (n = 185) and schizophrenia/schizoaffective disorders (n = 187). ECT was also used to treat many neurological disorders. Medical comorbidities were reported in 16% of all cases. Common coexisting conditions included developmental delay (n = 21) and autism (n = 18). Primary ECT indications included severe psychosis (n = 190), symptoms refractory to pharmacotherapy (n = 154), and suicidality (n = 153). ECT courses per patient ranged from 2 to 156. Duration averaged 91.89 ± 144.3 seconds. The most commonly reported induction agents were propofol and methohexital, and the most commonly reported paralytic agent was succinylcholine. Reported adverse events included headache, nausea, sedation, and short-term amnesia, as well as rare cases of benign dysrhythmias and prolonged seizure. Negative perception and diminished access to care result in treatment delays; thus, these children present in an advanced state of disease. In examining the details of modern ECT performed in 592 children, no major anesthetic morbidity was identified. Further study should start with retrospective analysis of anesthesia data during ECT to compare various effects of anesthesia medications and technique on adverse events and outcomes.

Isoflurane alone versus small dose propofol with isoflurane for removal of laryngeal mask airway in children-a randomized controlled trial.

OBJECTIVE: To compare the safety of laryngeal mask airway removal using two different deep anaesthesia techniques in paediatric patients. METHODS: The Randomized Control Trial was conducted at Aga Khan University Hospital, Karachi, from April 2012 to November 2013, and comprised patients aged 2-10 years scheduled for infraumbilical surgeries. Anaesthesia was induced with sevoflurane and later it was maintained by is oflurane, oxygen and nitrous oxide. The laryngeal mask airway was removed in the intervention group-I at 0.4 minimum alveolar concentration of isoflurane with propofol 1mg/kg. In the control group-II, it was removed at 1.2 minimum alveolar concentration of isoflurane alone. SPSS 19 was used for data analysis. RESULTS: Of the 50 patients, there were 25(50%) in each of the two groups. Overall, there were 46(92%) males and 4(8%) females. Incidence of airway obstruction and teeth clenching was significantly higher in group-II (p<0.05 each). Emergence duration was also significantly increased in group-II compared to group-I (p=0.001). The Post-Anaesthesia Care Unit stay timing was not significantly different between the groups (p=0.74). CONCLUSIONS: Laryngeal mask airway removal under deep anaesthetic technique of low-dose propofol with isoflurane was found to be associated with minimal adverse airway events than isoflurane alone in paediatric patients.

Effect of a Cognitive Aid on Reducing Sugammadex Use and Associated Costs: A Time Series Analysis.

BACKGROUND: The authors observed increased pharmaceutical costs after the introduction of sugammadex in our institution. After a request to decrease sugammadex use, the authors implemented a cognitive aid to help choose between reversal agents. The purpose of this study was to determine if sugammadex use changed after cognitive aid implementation. The authors' hypothesis was that sugammadex use and associated costs would decrease. METHODS: A cognitive aid suggesting reversal agent doses based on train-of-four count was developed. It was included with each dispensed reversal agent set and in medication dispensing cabinet bins containing reversal agents. An interrupted time series analysis was performed using pharmaceutical invoices and anesthesia records. The primary outcome was the number of sugammadex administrations. Secondary outcomes included total pharmaceutical acquisition costs of neuromuscular blocking drugs and reversal agents, adverse respiratory events, emergence duration, and number of neuromuscular blocking drug administrations. RESULTS: Before cognitive aid implementation, the number of sugammadex administrations was increasing at a monthly rate of 20 per 1,000 general anesthetics (P < 0.001). Afterward, the monthly rate was 4 per 1,000 general anesthetics (P = 0.361). One month after cognitive aid implementation, the number of sugammadex administrations decreased by 281 per 1,000 general anesthetics (95% CI, 228 to 333, P < 0.001). In the final study month, there were 509 fewer sugammadex administrations than predicted per 1,000 general anesthetics (95% CI, 366 to 653; P < 0.0001), and total pharmaceutical acquisition costs per 1,000 general anesthetics were $11,947 less than predicted (95% CI, $4,043 to $19,851; P = 0.003). There was no significant change in adverse respiratory events, emergence duration, or administrations of rocuronium, vecuronium, or atracurium. In the final month, there were 75 more suxamethonium administrations than predicted per 1,000 general anesthetics (95% CI, 32 to 119; P = 0.0008). CONCLUSIONS: Cognitive aid implementation to choose between reversal agents was associated with a decrease in sugammadex use and acquisition costs.

Efficacy Of Intravenous Lignocain Vs Sevoflurane In Prevention Of Coughing And Desaturation At Extubation In Children.

BACKGROUND: Inadvertent coughing and desaturation are the most commonly faced and feared respiratory complications in post-anaesthesia period. The study was done to compare the efficacy of intravenous lignocaine versus sevoflurane in prevention of coughing and desaturation at extubation in children less than 6 years of age. METHODS: This Randomized Control Trial was carried out from May 2013 to May 2016, at Combined Military Hospital Nowshera after obtaining approval from the hospital ethics committee (IREC-0003/5/13/Aneas). Children aged three months to six years undergoing surgical procedures requiring the placement of definitive airway were randomly assigned into two groups. Patients were anaesthetized by standardized balanced anaesthesia technique. In Group A (n=355), three minutes prior to extubation lignocaine 2% was used intravenously. In Group B (n=355), isoflurane was switched off, breathing circuit changed and sevoflurane started at minimum alveolar concentration (MAC 3-4%) for 3 minutes prior to extubation. Assessment for extubation was clinical. Oxygen saturation and severity of coughing were noted for 5 consecutive minutes, after extubation. RESULTS: In group-A, 156 patients were less than 2 years of age while in group-B, 135 patients were less than 2 years old. In group-A, 199 and in group-B, 220 children were 2-6 years of age respectively. Post stratification the p-value for weight was 0.17 (p-value >0.05) and t-statistic was 1.36. Post stratification p-value for gender was 0.12 (p-value>0.05) and chi square statistic was 2.49. Group A had more eventful extubation with 270 cases of cough (76%) as compared to group-B where it was noted in 199 cases (56%). Similarly, desaturation was observed in 85 cases in group-A (24%) as compared to 28 cases (8%) in group-B. The difference between the groups was statistically significant. CONCLUSIONS: Sevoflurane based anaesthetic vapours mixture causes statistical significant prevention from events like coughing episodes and desaturation in post-extubation in children less than six years of age undergoing elective surgery.

Regulatory Effect of General Anesthetics on Activity of Potassium Channels.

General anesthesia is an unconscious state induced by anesthetics for surgery. The molecular targets and cellular mechanisms of general anesthetics in the mammalian nervous system have been investigated during past decades. In recent years, K+ channels have been identified as important targets of both volatile and intravenous anesthetics. This review covers achievements that have been made both on the regulatory effect of general anesthetics on the activity of K+ channels and their underlying mechanisms. Advances in research on the modulation of K+ channels by general anesthetics are summarized and categorized according to four large K+ channel families based on their amino-acid sequence homology. In addition, research achievements on the roles of K+ channels in general anesthesia in vivo, especially with regard to studies using mice with K+ channel knockout, are particularly emphasized.

Anesthetic management of cesarean delivery for a parturient with Wilson's disease: A case report.

RATIONALE: Wilson's disease (WD), or hepatolenticular degeneration, is an autosomal recessive disorder with a prevalence of 1:50,000 to 1:100,000 live births. PATIENT CONCERNS: A 26-year-old primipara with WD was admitted to our hospital, due to awaiting delivery. Her main symptoms were slightly higher total bile acid (TBA) and bilateral depressed edema of lower limbs. DIAGNOSIS: She was at 38 weeks and 4 days of gestation with a 15-year history of WD, controlled with penicillamine in the past and replaced by zinc preparations from three months before pregnancy. OUTCOMES: General anesthesia was successfully administered for a female with WD undergoing cesarean delivery. LESSON: General anesthesia can be administered in an asymptomatic primigravida with WD. Appropriate anesthetics choice can effectively minimize the rates of complications and sequelae.

Trapping of Syntaxin1a in Presynaptic Nanoclusters by a Clinically Relevant General Anesthetic.

Propofol is the most commonly used general anesthetic in humans. Our understanding of its mechanism of action has focused on its capacity to potentiate inhibitory systems in the brain. However, it is unknown whether other neural mechanisms are involved in general anesthesia. Here, we demonstrate that the synaptic release machinery is also a target. Using single-particle tracking photoactivation localization microscopy, we show that clinically relevant concentrations of propofol and etomidate restrict syntaxin1A mobility on the plasma membrane, whereas non-anesthetic analogs produce the opposite effect and increase syntaxin1A mobility. Removing the interaction with the t-SNARE partner SNAP-25 abolishes propofol-induced syntaxin1A confinement, indicating that syntaxin1A and SNAP-25 together form an emergent drug target. Impaired syntaxin1A mobility and exocytosis under propofol are both rescued by co-expressing a truncated syntaxin1A construct that interacts with SNAP-25. Our results suggest that propofol interferes with a step in SNARE complex formation, resulting in non-functional syntaxin1A nanoclusters.

Acute Dystonic Reaction Following General Anesthetic Agent Use.

Background: A 36-year-old Thai female who underwent a thymectomy under general anesthesia developed acute abnormal movements in the craniofacial region immediately after awakening with preserved consciousness. Phenomenology: Intermittent abnormal movements included oculogyric crisis; tongue protrusion; blepharospasm; and oro-mandibular dystonia consisting of risus sardonicus, jaw opening, and right torticollis. Educational value: An acute dystonic reaction can be a complication of either single or combined general anesthetic agents.

General anesthetics protects against cardiac arrest-induced brain injury by inhibiting calcium wave propagation in zebrafish.

Cardiac arrest is a leading cause of death and disability worldwide. Although many victims are initially resuscitated, they often suffer from serious brain injury, even leading to a "persistent vegetative state". Therefore, it is need to explore therapies which restore and protect brain function after cardiac arrest. In the present study, using Tg (HuC:GCaMP5) zebrafish as a model, we found the zebrafish brain generated a burst of Ca2+ wave after cardiac arrest by in vivo time-lapse confocal imaging. The Ca2+ wave was firstly initiated at hindbrain and then sequentially propagated to midbrain and telencephalon, the neuron displayed Ca2+ overload after Ca2+ wave propagation. Consistent with this, our study further demonstrated neuronal apoptosis was increased in cardiac arrest zebrafish by TUNEL staining. The cardiac arrest-induced Ca2+ wave propagation can be prevented by general anesthetics such as midazolam or ketamine pretreatment. Moreover, midazolam or ketamine pretreatment dramatically decreased the neuronal apoptosis and improved the survival rate in CA zebrafish. Taken together, these findings provide the first in vivo evidence that general anesthetics pretreatment protects against cardiac arrest-induced brain injury by inhibiting calcium wave propagation in zebrafish.