The Anesthesiologists' Perception of Malignant Hyperthermia and Availability of Dantrolene in China: A Cross-Sectional Survey.

Background: Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists' understanding of MH in China. Methods: A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants' perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study. Results: Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (P=0.003), academic degree (P<0.001), hospital classification (P<0.001), and urban hierarchy (P<0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH. Conclusion: Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.

The feasibility of dexmedetomidine-led anesthesia maintenance strategy during major abdominal surgery.

Background: Dexmedetomidine is known for its selective action on α2-adrenoceptor sites and is recognized for its neuroprotective capabilities. It can improve postoperative cognitive function. Commonly used anesthetics, such as sevoflurane and propofol, have been reported to affect postoperative cognitive function. Therefore, it could be valuable to explore dexmedetomidine-led anesthesia strategy. This study was designed to assess the performance, safety, and effective infusion rate in anesthesia maintenance, to explore a feasible dexmedetomidine-led anesthesia maintenance protocol, and to provide a foundation for potential combined anesthesia. Methods: Thirty patients aged 18-60 years, classified as ASA I or II, undergoing abdominal surgery were involved. The anesthesia maintenance was achieved with dexmedetomidine, remifentanil and rocuronium. Dixon up-and-down sequential methodology was utilized to ascertain the ED50 of dexmedetomidine for maintaining Patient State Index (PSI) 25-40 (depth of stage III anesthesia). Intraoperative HR, BP and depth of anesthesia were monitored and controlled. The wake-up time from anesthesia, the incidence of intraoperative awareness and postoperative delirium, and the patients' satisfaction were assessed. Results: The results indicated that dexmedetomidine-led anesthesia could maintain the depth of stage III anesthesia during abdominal surgery. The ED50 and ED95 of dexmedetomidine infusion rates during anesthesia maintenance were 2.298 µg/kg·h (95%CI: 2.190-2.404 µg/kg·h) and 3.765 µg/kg·h (95%CI: 3.550-4.050 µg/kg·h). Continuous infusion of dexmedetomidine and 0.1-0.3 µg/kg·min remifentanil could maintain PSI 25-40, and provide appropriate anesthesia depth for abdominal surgery. Perioperative bradycardia and hypertension could be rapidly corrected with atropine and nitroglycerin. The median wake-up time after anesthesia was 4.8 min, the perioperative maximum HR had significant correlation with wake-up time and intraoperative dexmedetomidine dose. No intraoperative awareness and postoperative delirium occurred; the patients were satisfied with dexmedetomidine-led anesthesia. Conclusions: dexmedetomidine-led strategy could maintain stable depth of anesthesia throughout surgery, and the ED50 of dexmedetomidine infusion rates was 2.298 µg/kg·h. Intraoperative HR, BP and depth of anesthesia require monitoring, the bradycardia and hypertension could be rapidly corrected.

Epidemiological and clinical features of malignant hyperthermia: A scoping review.

Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of science databases were searched for studies that evaluated the epidemical and clinical characteristics of MH. A total of 37 studies were included in this review, of which 26 were related to epidemiology and 24 were associated with clinical characteristics. The morbidity of MH varied from 0.18 per 100 000 to 3.9 per 100 000. The mortality was within the range of 0%-18.2%. Identified risk factors included sex, age, disorders associated with MH, and others. The most frequent initial clinical signs included hyperthermia, sinus tachycardia, and hypercarbia. The occurrence of certain signs, such as hypercapnia, delayed first temperature measurement, and peak temperature were associated with poor outcomes. The epidemiological and clinical features of MH varied considerably and some risk factors and typical clinical signs were identified. The main limitation of this review is that the treatment and management strategies were not assessed sufficiently due to limited information.

Preoperative radiological indicators for prediction of difficult laryngoscopy in patients with atlantoaxial dislocation.

Background: Difficult airway remains a great challenge in patients with atlantoaxial dislocation (AAD). Preoperative evaluation and reliable prediction are required to facilitate the airway management. We aimed to screen out reliable radiological indicators for prediction of difficult laryngoscopy in patients with AAD. Methods: A retrospective nested case-control study within a single center longitudinal AAD cohort was conducted to investigate the radiological indicators. All the patients with difficult laryngoscopy from 2010 to 2021 were enrolled as the difficult laryngoscopy group. Others in the cohort without difficult laryngoscopy were randomly selected as the non-difficult laryngoscopy group by individually matching with the same gender, same surgery year, and similar age (±5 years) at a ratio of 6:1. Radiological data on preoperative lateral X-ray images between the two groups were compared. Bivariate logistic regression model was applied to screen out the independent predictive indicators and calculate the odds ratios of indicators associated with difficult laryngoscopy. Receiver operating characteristic curve and area under the curve (AUC) were used to describe the discrimination ability of indicators. Results: A total of 154 patients were finally analyzed in this study. Twenty-two patients with difficult laryngoscopy and matched with 132 controls. Four radiological parameters showed significant difference between the two groups. Among which, ΔC1C2D (the difference of the distance between atlas and axis in the neutral and extension position), owned the largest AUC. Conclusions: ΔC1C2D could be a valuable radiologic predictor for difficult laryngoscopy in patients with AAD.

Evaluation of a New Method of Sciatic Nerve Block: A Prospective Pilot Study.

Purpose: The location of the sciatic nerve deep within the thigh tissue makes it challenging to locate while the patient is in a supine position. The posterior intermuscular septum of the thigh, which encircles the posterior surface of the adductor magnus muscle (AMM), is where the sciatic nerve is located. Our hypothesis was that administering local anesthetic injections into this area could block the sciatic nerve. Therefore, our aim was to evaluate the effectiveness of sciatic nerve block achieved by injecting local anesthetic into the posterior intermuscular septum of the thigh, named the AMM approach. Methods: Twenty-six patients undergoing total knee arthroplasty were included in the study. We performed an ultrasound-guided sciatic nerve block by injecting 20 mL of 0.25% ropivacaine into the posterior surface of the adductor magnus muscle, using the AMM approach. Additionally, we administered a femoral nerve block with 20 mL of 0.4% ropivacaine. We assessed the sensory and motor effects of the blockade in the operated lower limb and recorded postoperative pain scores at 0, 4, 8, 12, 24, and 48 hours after the operation. Results: The AMM approach successfully block the sciatic nerve in all 26 patients. The onset of the sensory and motor blockades was achieved within 5.4 ± 1.9 min and 8.7 ± 3.5 min, respectively. We achieved a satisfactory position with the first puncture in 19 of 26 patients (73.1%). The muscle strength of the tibialis anterior immediately after surgery was 4 (ranging from 2 to 5). Additional rescue analgesics were required in 5 of the 26 patients (19.2%) during the first 24 hours postoperatively. Conclusion: The AMM approach is an innovative and effective method for sciatic nerve block. When combined with simultaneous femoral nerve block in patients undergoing total knee arthroplasty, it provides a useful analgesic treatment option.

Construction and analysis of circular RNA-associated competing endogenous RNA network in the hippocampus of aged mice for the occurrence of postoperative cognitive dysfunction.

Circular RNAs are highly stable single-stranded circular RNAs and enriched in the brain. Previous studies showed that circRNAs, as part of competing endogenous RNAs (ceRNAs) network, play an important role in neurodegenerative and psychiatric diseases. However, the mechanism of circRNA-related ceRNA networks in postoperative cognitive dysfunction (POCD) has not been elucidated yet. POCD usually occurs in elderly patients and is characterized by hippocampal dysfunction. Here, aged C57BL/6 mice were subjected to exploratory laparotomy under sevoflurane anesthesia, and this POCD model was verified by Morris water maze test. Whole-transcriptome sequencing was performed on the hippocampus of control group (Con) and surgery group. One hundred and seventy-seven DEcircRNAs, 221 DEmiRNAs and 2,052 DEmRNAs were identified between two groups. A ceRNA network was established with 92 DEcircRNAs having binding sites with 76 DEmiRNAs and 549 target DEmRNAs. In functional enrichment analysis, a pathological pattern of POCD was highlighted in the ceRNA network: Abnormal metabolic process in neural cells, including oxygen metabolism, could promote apoptosis and then affect the synaptic function, which may undermine the neural plasticity and eventually lead to changes in cognitive function and other behavioral patterns. In conclusion, this specific ceRNA network of circRNAs-miRNAs-mRNAs has provided novel insights into the regulatory mechanisms of POCD and revealed potential therapeutic gene targets.

Whole-transcriptome sequencing identifies neuroinflammation, metabolism and blood-brain barrier related processes in the hippocampus of aged mice during perioperative period.

AIM: Perioperative neurocognitive disorders (PND) occur frequently after surgery and anesthesia, especially in aged patients. Previous studies have shown multiple PND related mechanisms in the hippocampus; however, their relationships remain unclear. Meanwhile, the perioperative neuropathological processes are sophisticated and changeable, single period study could not reveal the accurate mechanisms. Thus, multiperiod whole-transcriptome study is necessary to elucidate the gene expression patterns during perioperative period. METHODS: Aged C57BL/6 mice were subjected to exploratory laparotomy under sevoflurane anesthesia. Whole-transcriptome sequencing (RNA-seq analysis) was performed on the hippocampi from control condition (Con), 30 min (Day0), 2 days (Day2), and 7 days (Day7) after surgery. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses, quantitative real-time PCR, immunofluorescence, and fear conditioning test were also performed to elucidate the pathological processes and modulation networks during the period. RESULTS: Through RNA-seq analysis, 328, 3597, and 4179 differentially expressed genes (DEGs) were screened out in intraoperative period (Day0 vs. Con), early postoperative period (Day2 vs. Day0), and late postoperative period (Day7 vs. Day2). The involved GO biological processes were divided into 9 categories, and positive-regulated processes were more than negative-regulated ones. Seventy-four transcription factors were highlighted. The potential synaptic and neuroinflammatory pathways were constructed for Neurotransmitter, Synapse and Neuronal alteration categories with 9 genes (Htr1a, Rims1, and Ezh2, etc.). The metabolic and mitochondrial pathways were constructed for metabolism, oxidative stress, and biological rhythm categories with 9 genes (Gpld1, Sirt1, and Cry2, etc.). The blood-brain barrier and neurotoxicity related pathways were constructed for blood-brain barrier, neurotoxicity, and cognitive function categories with 10 genes (Mmp2, Itpr1, and Nrf1, etc.). CONCLUSION: The results revealed gene expression patterns and modulation networks in the aged hippocampus during perioperative period, which provide insights into overall mechanisms and potential therapeutic targets for prevention and treatment of perioperative central nervous system diseases, such as PND, from the genetic level.

lncRNAs Are Involved in Sevoflurane Anesthesia-Related Brain Function Modulation through Affecting Mitochondrial Function and Aging Process.

Long noncoding RNAs (lncRNAs) play important roles in brain function modulation and neurodegenerative diseases. However, whether lncRNA regulations are involved in the mechanisms of perioperative neurocognitive disorders, especially in anesthesia-related brain dysfunction, remain unknown. Therefore, we explored the expression and regulation pattern profiles of lncRNAs in the hippocampus of aged rats after sevoflurane anesthesia. Three lncRNAs and 772 protein-coding genes were identified by microarray analysis and evidenced by in vitro and in vivo experiments as differentially expressed. Functional annotation and differentially expressed- (DE-) lncRNA-mRNA coexpression networks reveal that DE-lncRNAs are associated with mitochondrial dysfunction and oxidative stress, aging-related metabolism alterations, DNA damage, and apoptosis, as well as neurodegenerative features during sevoflurane anesthesia. These results suggest that lncRNAs play roles in general anesthesia-related brain function modulation during the perioperative context and provide insights into the lncRNA-related modulation mechanisms and targets.

DNA Methylation Manipulation of Memory Genes Is Involved in Sevoflurane Induced Cognitive Impairments in Aged Rats.

DNA methylation is an essential epigenetic mechanism involving in gene transcription modulation. An age-related increase in promoter methylation has been observed for neuronal activity and memory genes, and participates in neurological disorders. However, the position and precise mechanism of DNA methylation for memory gene modulation in anesthesia related cognitive impairment remained to be determined. Here, we studied the effects of sevoflurane anesthesia on the transcription of memory genes in the aged rat hippocampus. Then, we investigated changes in DNA methylation of involved genes and verified whether dysregulated DNA methylation would contribute to anesthesia induced cognitive impairment. The results indicated that sevoflurane anesthesia down-regulated the mRNA and protein levels of three memory genes, Arc, Bdnf, and Reln, which were accompanied with promoter hypermethylation and increased Dnmt1, Dnmt3a, and Mecp2 expression, and finally impaired hippocampus dependent memory. Furthermore, inhibition of DNA hypermethylation by 5-Aza rescued sevoflurane induced memory gene expression decrease and cognitive impairment. These findings provide an epigenetic understanding for the pathophysiology of cognitive impairment induced by general anesthesia in aged brain.

Genome-Wide Screen of the Hippocampus in Aged Rats Identifies Mitochondria, Metabolism and Aging Processes Implicated in Sevoflurane Anesthesia.

Previous studies have shown multiple mechanisms and pathophysiological changes after anesthesia, and genome-wide studies have been implemented in the studies of brain aging and neurodegenerative diseases. However, the genome-wide gene expression patterns and modulation networks after general anesthesia remains to be elucidated. Therefore, whole transcriptome microarray analysis was used to explore the coding gene expression patterns in the hippocampus of aged rats after sevoflurane anesthesia. Six hundred and thirty one upregulated and 183 downregulated genes were screened out, then 44 enriched terms of biological process, 16 of molecular function and 18 of the cellular components were identified by Gene Ontology (GO) and KEGG analysis. Among them, oxidative stress, metabolism, aging, and neurodegeneration were the most enriched biological processes and changed functions. Thus, involved genes of these processes were selected for qPCR verification and a good consistency was confirmed. The potential signaling pathways were further constructed including mitochondrion and oxidative stress-related Hifs-Prkcd-Akt-Nfe2l2-Sod1 signaling, multiple metabolism signaling (Scd2, Scap-Hmgcs2, Aldh18a1-Glul and Igf1r), as well as aging and neurodegeneration related signaling (Spidr-Ercc4-Cdkn1a-Pmaip1 and Map1lc3b). These results provide potential therapeutic gene targets for brain function modulation and memory formation process after inhaled anesthesia in the elderly, which could be valuable for preventing postoperative brain disorders and diseases, such as perioperative neurocognitive disorders (PND), from the genetic level in the future.

Metastatic leiomyosarcoma presenting as a lung mass with left atrial extension: case report and anesthetic management.

INTRODUCTION: Lung metastasis of leiomyosarcoma that protrudes into the left atrium is an extremely rare condition. Severe complications may occur that prominently increase the mortality during the perioperative period. Currently, the anesthetic management reports are limited and there is no generally acknowledged algorithm available. CASE PRESENTATION: A 67-year-old man presented with cough and dyspnea for 10 days. Workup revealed bilateral pulmonary effusion. Transthoracic echocardiography showed a large mass in the left atrium. Urgent surgical resection under cardiopulmonary bypass was performed. We focused on oxygenation improvement and cardiac function management by applying protective ventilation with low positive end expiratory pressure, low dose inotropic agents, and other methods to maintain stable homeostasis. Results of biopsy established a diagnosis of metastatic leiomyosarcoma. CONCLUSION: We reported a case of metastatic leiomyosarcoma presenting as a lung mass with left atrial extension and anesthetic management during surgical resection. Treating acute heart failure and refractory hypoxemia was the key focus perioperatively.