A systematic review on the use of sevoflurane in the management of status asthmaticus in adults.

BACKGROUND: To conduct a systematic review looking into the use of sevoflurane in the management of status asthmaticus (SA) in adults. METHODS: We performed a systematic search on PubMed, EMBASE, and The Cochrane Library - CENTRAL through 23rd August 2023, restricting to studies reported in English. We included studies reporting use of sevoflurane in asthmatics beyond its use as an anaesthetic agent in surgeries i.e. in the emergency department (ED) and critical care setting, and focused on patient's clinical parameters, ventilation pressures and weaning of invasive ventilation. RESULTS: A total of 13 publications fulfilled the inclusion criteria, comprising of 18 cases. All publications were of case reports/ series and conference abstracts, and no randomised trials were available. Most patients required intubation despite best medical management before sevoflurane administration, and high airway pressures and respiratory acidosis were apparent. There was significant heterogeneity regarding severity of asthma, treatment instituted, and the delivery, duration and concentration of sevoflurane administered. Many of the studies also did not quantify the changes in parameters pre- and post-sevoflurane. Sixteen patients experienced improvements in clinical status with sevoflurane administration-one required escalation to extracorporeal membrane oxygenation (ECMO), and another did not survive. CONCLUSION: The systematic review suggests sevoflurane can be a valuable treatment option in SA. As these cases are rare and heterogenous, further prospective case series are needed to support this.

Opioid-free anaesthesia reduces postoperative nausea and vomiting after thoracoscopic lung resection: a randomised controlled trial.

BACKGROUND: Intraoperative opioid use has a positive relationship with postoperative nausea and vomiting (PONV), and opioid-free anaesthesia (OFA) might reduce PONV. We investigated whether OFA compared with opioid-based anaesthesia would reduce PONV during the first 2 postoperative days among patients undergoing thoracoscopic lung resection. METHODS: In this randomised controlled trial, 120 adult patients were randomly assigned (1:1, stratified by sex) to receive either OFA with esketamine, dexmedetomidine, and sevoflurane, or opioid-based anaesthesia with sufentanil and sevoflurane. A surgical pleth index (SPI) of 20-50 was applied for intraoperative analgesia provision. All subjects received PONV prophylaxis (dexamethasone and ondansetron) and multimodal analgesia (flurbiprofen axetil, ropivacaine wound infiltration, and patient-controlled sufentanil). The primary outcome was the occurrence of PONV during the first 48 h after surgery. RESULTS: The median age was 53 yr and 66.7% were female. Compared with opioid-based anaesthesia, OFA significantly reduced the incidence of PONV (15% vs 31.7%; odds ratio [OR]=0.38, 95% confidence interval [CI], 0.16-0.91; number needed to treat, 6; P=0.031). Secondary and safety outcomes were comparable between groups, except that OFA led to a lower rate of vomiting (OR=0.23, 95% CI, 0.08-0.77) and a longer length of PACU stay (median difference=15.5 min, 95% CI, 10-20 min). The effects of OFA on PONV did not differ in the prespecified subgroups of sex, smoking status, and PONV risk scores. CONCLUSIONS: In the context of PONV prophylaxis and multimodal analgesia, SPI-guided opioid-free anaesthesia halved the incidence of PONV after thoracoscopic lung resection, although it was associated with a longer stay in the PACU. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200059710).

Immunotherapeutic Properties of Dexmedetomidine on Pain Management and Cardiovascular Function in Videolaparoscopic Cholecystectomies: A Randomized, Two-Arm, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND: Laparoscopy represented one of the most innovative surgical techniques approached in the surgery field. Dexmedetomidine association with general anesthesia promotes the response control to trauma by altering the neuroinflammatory reflex, provides better clinical outcomes in the postoperative period and reduces the excessive use of drugs with risk for addiction. This trial aims to evaluate the potential drug treatment of dexmedetomidine on organic function, with the targets in neuroinflammation, perioperative pain control and blood pressure measurements in a medium-sized surgical model. METHODS: Fifty-two patients were randomized in two groups: Sevoflurane and Dexmedetomidine - A (dexmedetomidine infusion [1 µg/kg loading, .2-.5 µg/kg/h thereafter]) vs Sevoflurane and Saline .9% - B. Three blood samples were collected at three times: before surgery, 4 to 6 hours after surgery and 24 hours postoperatively. The primary outcome was inflammatory and endocrine mediators dosage analisys. Finally, we evaluated pain and opioid use as secondary outcomes, also the hemodynamic values. RESULTS: In Dexmedetomidine group A, a reduction of Interleukin 6 was found during 4-6 hours after surgery. A reduction of IL-10 was noted in the measurement of its values 24 hours after the procedure, with statistical significance. Also, systolic and diastolic blood pressure, as well heart rate were attenuated, and there was a lower incidence of pain and opioid consumption in the first postoperative hour (P < .0001) in the anesthetic recovery room. CONCLUSIONS: Dexmedetomidine provided anti-inflammatory activity, sympatholytic effect and analgesia with cardiovascular safety. It reinforces the therapeutic nature of highly selective α2-adrenergic agonists when combined within anesthetic interventions.

Effects of sevoflurane on lung epithelial permeability in experimental models of acute respiratory distress syndrome.

BACKGROUND: Preclinical studies in acute respiratory distress syndrome (ARDS) have suggested that inhaled sevoflurane may have lung-protective effects and clinical trials are ongoing to assess its impact on major clinical outcomes in patients with ARDS. However, the underlying mechanisms of these potential benefits are largely unknown. This investigation focused on the effects of sevoflurane on lung permeability changes after sterile injury and the possible associated mechanisms. METHODS: To investigate whether sevoflurane could decrease lung alveolar epithelial permeability through the Ras homolog family member A (RhoA)/phospho-Myosin Light Chain 2 (Ser19) (pMLC)/filamentous (F)-actin pathway and whether the receptor for advanced glycation end-products (RAGE) may mediate these effects. Lung permeability was assessed in RAGE-/- and littermate wild-type C57BL/6JRj mice on days 0, 1, 2, and 4 after acid injury, alone or followed by exposure at 1% sevoflurane. Cell permeability of mouse lung epithelial cells was assessed after treatment with cytomix (a mixture of TNFɑ, IL-1ß, and IFNγ) and/or RAGE antagonist peptide (RAP), alone or followed by exposure at 1% sevoflurane. Levels of zonula occludens-1, E-cadherin, and pMLC were quantified, along with F-actin immunostaining, in both models. RhoA activity was assessed in vitro. RESULTS: In mice after acid injury, sevoflurane was associated with better arterial oxygenation, decreased alveolar inflammation and histological damage, and non-significantly attenuated the increase in lung permeability. Preserved protein expression of zonula occludens-1 and less increase of pMLC and actin cytoskeletal rearrangement were observed in injured mice treated with sevoflurane. In vitro, sevoflurane markedly decreased electrical resistance and cytokine release of MLE-12 cells, which was associated with higher protein expression of zonula occludens-1. Improved oxygenation levels and attenuated increase in lung permeability and inflammatory response were observed in RAGE-/- mice compared to wild-type mice, but RAGE deletion did not influence the effects of sevoflurane on permeability indices after injury. However, the beneficial effect of sevoflurane previously observed in wild-type mice on day 1 after injury in terms of higher PaO2/FiO2 and decreased alveolar levels of cytokines was not found in RAGE-/- mice. In vitro, RAP alleviated some of the beneficial effects of sevoflurane on electrical resistance and cytoskeletal rearrangement, which was associated with decreased cytomix-induced RhoA activity. CONCLUSIONS: Sevoflurane decreased injury and restored epithelial barrier function in two in vivo and in vitro models of sterile lung injury, which was associated with increased expression of junction proteins and decreased actin cytoskeletal rearrangement. In vitro findings suggest that sevoflurane may decrease lung epithelial permeability through the RhoA/pMLC/F-actin pathway.

Effective dose of ephedrine for treatment of hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age: a multicentre randomised, controlled, open label, dose escalation trial.

BACKGROUND: The recommended dose of ephedrine in adults (0.1 mg kg-1) frequently fails to treat hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age. The aim of this study was to determine the optimal dose of ephedrine in this population for the treatment of hypotension after induction of general anaesthesia with sevoflurane. METHODS: We conducted a multicentre, prospective, randomised, open-label, controlled, dose-escalation trial. Subjects were randomised if presenting a >20% change from baseline in MAP. Six cohorts of 20 subjects each were enrolled. Ten subjects in the first cohort received 0.1 mg kg-1 i. v. (reference dose). For each subsequent cohort, 10 subjects were assigned to the next higher dose (consecutively 0.6, 0.8, 1, 1.2, and 1.4 mg kg-1 i. v.), and the other subjects were assigned to one or more doses already investigated in previous cohorts. The primary outcome was the return of MAP to >80% of baseline at least once within 10 min after ephedrine administration. RESULTS: A total of 119 infants (25% females), with a mean age (standard deviation) of 2.7 (1.3) months, received their allocated dose of ephedrine. The optimal dose of ephedrine was 1.2 mg kg-1, with a percentage of success of 65.5% (95% confidence interval, 35.6-86.4). The doses of ephedrine investigated did not induce adverse events. CONCLUSIONS: Doses of ephedrine much higher (∼10-fold) than those used in adults are necessary in neonates and infants for the treatment of hypotension after induction of general anaesthesia with sevoflurane. CLINICAL TRIAL REGISTRATION: NCT02384876.

The Anti-Inflammatory and Antioxidant Effects of Propofol and Sevoflurane in Children With Cyanotic Congenital Heart Disease.

OBJECTIVE: The authors aimed to compare the anti-inflammatory and antioxidant effects of propofol and sevoflurane in children with cyanotic congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, randomized, double-blind study. SETTING: Single center, university hospital. PARTICIPANTS: Children ages 1-10 years with CCHD undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Children were randomized to receive general anesthesia with either sevoflurane (group S) or propofol (group P). Systemic inflammatory response syndrome (SIRS) occurrence was assessed at the end of the surgery and at the sixth, 12th, and 24th postoperative hours. Blood samples were obtained at 4 times: after anesthesia induction (T0), after release of the aortic cross-clamp (T1), at the end of the surgery (T2), and at the postoperative 24th hour (T3). The serum levels of interleukin 6 and tumor necrosis factor alpha, and the total antioxidant status (TAS) and total oxidant status, were analyzed. RESULTS: SIRS was more common in group S than in group P at all times (p = 0.020, p = 0.036, p = 0.004, p = 0.008). There were no significant differences between the groups in the mean tumor necrosis factor alpha and interleukin 6 levels at any time. The TAS level at T2 was higher in group P than group S (p = 0.036). The serum TAS level increased at T2 compared with T0 in group P, but it decreased in group S (p = 0.041). CONCLUSION: The results showed that propofol provided a greater antioxidant effect and reduced SIRS postoperatively more than sevoflurane in children with CCHD undergoing cardiac surgery.

Needleless inhaled anesthesia with sevoflurane: Advantages of a simplified approach for children with spinal muscular atrophy undergoing intrathecal administration of nusinersen.

BACKGROUND: Intrathecal nusinersen administration, a fundamental step in the treatment of spinal muscular atrophy, is challenging in children. AIMS: This retrospective monocentric analysis of prospectively collected data evaluated the feasibility of needleless general anesthesia exclusively with sevoflurane, without imaging guidance, for children undergoing nusinersen administration in a 24-month period. METHODS: Clinical data included demographics, type of spinal muscular atrophy, presence and severity of scoliosis. Primary outcome was defined by the number of predefined sentinel adverse events related to anesthesia. Secondary outcomes were assessed by duration of the procedure, number of lumbar puncture attempts, and number of failures. Other measures included number and type of moderate, minor and minimal adverse events, as well as number and type of puncture-related adverse events. RESULTS: 116 patients (mean age: 8.7 (SD 6.9) years; with scoliosis: 49.1%) underwent 250 lumbar punctures; two cases of prolonged desaturation, considered as sentinel adverse events, (0.8%) were recorded during anesthesia (primary outcome). None of the patients underwent orotracheal intubation nor required an unplanned admission in the Pediatric Intensive Care Unit. No patient required an unplanned or prolonged hospitalization after the procedure. Mean number of puncture attempts was 1.6 (SD 1.3), and mean duration of the procedure was 14.1 (SD 8.3) minutes. No failure in the drug administration occurred (secondary outcomes). CONCLUSION: In this single-center experience, needleless general anesthesia with inhaled sevoflurane without imaging guidance has been shown to be feasible for children with spinal muscular atrophy undergoing lumbar puncture for nusinersen administration.

S-ketamine promotes postoperative recovery of gastrointestinal function and reduces postoperative pain in gynecological abdominal surgery patients: a randomized controlled trial.

BACKGROUND: This prospective randomized controlled study was designed to evaluate the effect of S-ketamine with sufentanil given intraoperatively and postoperatively on recovery of gastrointestinal (GI) function and postoperative pain in gynecological patients undergoing open abdomen surgery. METHODS: One hundred gynecological patients undergoing open abdomen surgery were randomized into an S-ketamine group (group S) or placebo group (0.9% saline; group C). Anesthesia was maintained with S-ketamine, sevoflurane, and remifentanil-propofol target-controlled infusion in group S and with sevoflurane and remifentanil-propofol target-controlled infusion in group C. All patients were connected to patient-controlled intravenous analgesia (PCIA) pump at the end of the surgery with sufentanil, ketorolac tromethamine, and tropisetron in group C and additional S-ketamine in group S. The primary outcome was the time of first postoperative flatus, and the secondary outcome was postoperative pain score of patients. Postoperative sufentanil consumption within the first postoperative 24 h and adverse events such as nausea and vomiting were recorded. RESULTS: The time of first postoperative flatus in group S was significantly shorter (mean ± SD, 50.3 ± 13.5 h) than that in group C (mean ± SD, 56.5 ± 14.3 h, p = 0.042). The patient's visual analog scale (VAS) pain score 24 h after surgery at rest was significantly lower in group S than in group C (p = 0.032). There were no differences in sufentanil consumption within the first postoperative 24 h, postoperative complications related to PCIA between the two groups. CONCLUSIONS: S-ketamine accelerated postoperative GI recovery and reduced 24 h postoperative pain in patients undergoing open gynecological surgery. TRIAL REGISTRATION: ChiCTR2200055180. Registered on 02/01/2022. It is a secondary analysis of the same trial.

Experimental and Clinical Aspects of Sevoflurane Preconditioning and Postconditioning to Alleviate Hepatic Ischemia-Reperfusion Injury: A Scoping Review.

Ischemia-reperfusion injury (IRI) is an inflammatory process inherent in organ transplantation procedures. It is associated with tissue damage and, depending on its intensity, can impact early graft function. In liver transplantation (LT), strategies to alleviate IRI are essential in order to increase the use of extended criteria donor (ECD) grafts, which are more susceptible to IRI, as well as to improve postoperative graft and patient outcomes. Sevoflurane, a commonly used volatile anesthetic, has been shown to reduce IRI. This scoping review aims to give a comprehensive overview of the existing experimental and clinical data regarding the potential benefits of sevoflurane for hepatic IRI (HIRI) and to identify any gaps in knowledge to guide further research. We searched Medline and Embase for relevant articles. A total of 380 articles were identified, 45 of which were included in this review. In most experimental studies, the use of sevoflurane was associated with a significant decrease in biomarkers of acute liver damage and oxidative stress. Administration of sevoflurane before hepatic ischemia (preconditioning) or after reperfusion (postconditioning) appears to be protective. However, in the clinical setting, results are conflicting. While some studies showed a reduction of postoperative markers of liver injury, the benefit of sevoflurane on clinical outcomes and graft survival remains unclear. Further prospective clinical trials remain necessary to assess the clinical relevance of the use of sevoflurane as a protective factor against HIRI.

The neuroprotective mechanism of sevoflurane in rats with traumatic brain injury via FGF2.

BACKGROUND: Traumatic brain injury (TBI) is a kind of acquired brain injury, which is caused by external mechanical forces. Moreover, the neuroprotective role of sevoflurane (Sevo) has been identified in TBI. Therefore, this research was conducted to figure out the mechanism of Sevo in TBI via FGF2. METHODS: The key factors of neuroprotective effects of Sevo in TBI rats were predicted by bioinformatics analysis. A TBI model was induced on rats that then inhaled Sevo for 1 h and grouped via lentivirus injection. Modified Neurological Severity Score was adopted to evaluate neuronal damage in rats, followed by motor function and brain water content measurement. FGF2, EZH2, and HES1 expression in brain tissues was evaluated by immunofluorescence staining, and expression of related genes and autophagy factors by RT-qPCR and Western blot analysis. Methylation-specific PCR was performed to assess HES1 promoter methylation level, and ChIP assay to detect the enrichment of EZH2 in the HES1 promoter. Neuronal damage was assessed by cell immunofluorescence staining, and neuronal apoptosis by Nissl staining, TUNEL staining, and flow cytometry. RESULTS: Sevo diminished brain edema, improved neurological scores, and decreased neuronal apoptosis and autophagy in TBI rats. Sevo preconditioning could upregulate FGF2 that elevated EZH2 expression, and EZH2 bound to the HES1 promoter to downregulate HES1 in TBI rats. Also, FGF2 or EZH2 overexpression or HES silencing decreased brain edema, neurological deficits, and neuronal autophagy and apoptosis in Sevo-treated TBI rats. CONCLUSIONS: Our results provided a novel insight to the neuroprotective mechanism of Sevo in TBI rats by downregulating HES1 via FGF2/EZH2 axis activation.

Effect of sevoflurane preconditioning on sleep reintegration after alteration by lipopolysaccharide.

Despite extensive evidence on the organ protective effects of sevoflurane, its effect on disturbed sleep remains unclear. We hypothesised that sevoflurane preconditioning positively impacts disturbed sleep caused by systemic inflammation. A prospective, randomised laboratory investigation was conducted in C57BL/6J mice. A mouse model of lipopolysaccharide (LPS)-induced systemic inflammation was employed to investigate the effects of sevoflurane on sleep recovery. Symptom recovery was evaluated through electroencephalography/electromyography (EEG/EMG) and histological studies. The mice were exposed to 2% sevoflurane before and after peritoneal injection of LPS. The EEG and EMG were recorded for 24 h after the procedure. Brain tissue was harvested after the sevoflurane/LPS procedure and was immunostained using individual antibodies against choline acetyltransferase (ChAT) and Fos. The ChAT-positive and ChAT/Fos double-positive cells were analysed quantitatively in the pedunculopontine tegmental nucleus and laterodorsal tegmental nucleus (PPTg/LDTg). Compared with control mice, mice preconditioned with sevoflurane but not post-conditioned showed a significant increase in rapid eye movement (REM) sleep during EEG recording following the LPS challenge. They also demonstrated a shorter REM latency, indicating an early recovery from LPS-altered sleep. The bouts of REM episodes were retained with sevoflurane preconditioning. More ChAT/Fos double-positive cells were observed in the PPTg/LDTg in the sevoflurane preconditioning plus LPS group than in the LPS-only group. Sevoflurane preconditioning promotes recovery from altered sleep induced by systemic inflammation. Activation of PPTg/LDTg is considered a mechanism underlying sleep reintegration. The recovery phenomenon shows potential for clinical application in cases of sleep disturbances induced by systemic inflammation.

Inflammatory Biomarker Levels After Propofol or Sevoflurane Anesthesia: A Meta-analysis.

BACKGROUND: The perioperative inflammatory response may be implicated in adverse outcomes including neurocognitive dysfunction and cancer recurrence after oncological surgery. The immunomodulatory role of anesthetic agents has been demonstrated in vitro; however, its clinical relevance is unclear. The purpose of this meta-analysis was to compare propofol and sevoflurane with respect to biomarkers of perioperative inflammation. The secondary aim was to correlate markers of inflammation with clinical measures of perioperative cognition. METHODS: Databases were searched for randomized controlled trials examining perioperative inflammation after general anesthesia using propofol compared to sevoflurane. Inflammatory biomarkers investigated were interleukin (IL)-6, IL-10, tissue necrosis factor alpha (TNF-α), and C-reactive protein (CRP). The secondary outcome was incidence of perioperative neurocognitive disorders. Meta-analysis with metaregression was performed to determine the difference between propofol and sevoflurane. RESULTS: Twenty-three studies were included with 1611 participants. Studies varied by surgery type, duration, and participant age. There was an increase in the mean inflammatory biomarker levels following surgery, with meta-analysis revealing no difference in effect between propofol and sevoflurane. Heterogeneity between studies was high, with surgery type, duration, and patient age contributing to the variance across studies. Only 5 studies examined postoperative cognitive outcomes; thus, a meta-analysis could not be performed. Nonetheless, of these 5 studies, 4 reported a reduced incidence of cognitive decline associated with propofol use. CONCLUSIONS: Surgery induces an inflammatory response; however, the inflammatory response did not differ as a function of anesthetic technique. This absence of an effect suggests that patient and surgical variables may have a far more significant impact on the postoperative inflammatory responses than anesthetic technique. The majority of studies assessing perioperative cognition in older patients reported a benefit associated with the use of propofol; however, larger trials using homogenous outcomes are needed to demonstrate such an effect.

A Round Trip: The Japanese Contribution to the Development of Sevoflurane.

Sevoflurane was first synthesized independently by Richard Wallin and Bernard Regan at Travenol Laboratories Incorporated and Ross Terrell and Louise Croix at Airco, Inc in the late 1960s, and subsequent animal studies and a phase-1 human trial of the agent published in 1981 showed promising results. Further research in the United States was halted, however, because of concerns regarding potential nephrotoxicity and the introduction of less degradable alternatives. Interest in sevoflurane resumed in Japan when Maruishi Pharmaceutical Company, Limited (Ltd) (Maruishi) decided to continue its development in 1982. They secured approval by the Japanese Ministry of Health, Labor and Welfare for its clinical use in January 1990. Because of its low blood:gas partition coefficient and resulting rapid action, sevoflurane quickly became the anesthetic of choice of Japanese anesthesiologists. In 1992 Abbott Laboratories, now AbbVie, Inc (Abbott, North Chicago, IL) finalized a licensing agreement with Maruishi to seek the US Food and Drug Administration approval for sevoflurane sales in the United States. Approved in June 1995, sevoflurane is now marketed by Abbott in 120 countries and has been administered >120 million times. This report details the Japanese contribution to the development of sevoflurane.

Sevoflurane inhibits the malignant phenotypes of glioma through regulating miR-146b-5p/NFIB axis.

PURPOSE: Sevoflurane is a common used inhaled anesthetic that was reported to regulate the progression of multiple cancers. Here, we aimed to investigate the function and regulatory mechanism underlying sevoflurane in glioma cells. METHODS: A172 and U251 cells were treated with different concentrations of sevoflurane. Colony formation, EdU satining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and transwell assays were performed to evaluate cell proliferation, apoptosis, migration and invasion, respectively. Circ_VCAN, microRNA-146b-5p (miR-146b-5p) and nuclear factor I B (NFIB) expression levels were assessed by real-time quantitative PCR (RT-qPCR) or western blot. Bioinformatics analysis and dual-luciferase reporter assay were applied to evaluate the correlation between miR-146b-5p and circ_VCAN or NFIB. A xenograft glioma mice model was established to verify the effect of sevoflurane on tumor growth in vivo. RESULTS: Sevoflurane (Sev) inhibited proliferation, migration, invasion, and elevated apoptosis of A172 and U251 cells. Sevoflurane treatment inhibited the expression of circ_VCAN and NFIB, but elevated the expression of miR-146b-5p in glioma cells. Overexpression of circ_VCAN alleviated the inhibition effects of sevoflurane on the malignant phenotypes of glioma in vitro and in vivo. Besides, miR-146b-5p is a target of circ_VCAN and negatively regulated NFIB expression. Overexpression of miR-146b-5p partly reversed the effects of circ_VCAN in Sev-treated glioma cells. Furthermore, miR-146b-5p deletion enhanced glioma progression in sevoflurane treated glioma cells by targeting NFIB. Moreover, circ_VCAN could upregulate NFIB expression by sponging miR-146b-5p in Sev-treated glioma cells. CONCLUSION: Sevoflurane alleviated proliferation, migration and invasion, but enhanced apoptosis of glioma cells through regulating circ_VCAN/miR-146b-5p/NFIB axis.

Application of Propofol Target-Controlled Infusion for Optimized Hemodynamic Status in ESRD Patients Receiving Arteriovenous Access Surgery: A Randomized Controlled Trial.

Background and Objectives: End-stage renal disease (ESRD) is associated with increased anesthetic risks such as cardiovascular events resulting in higher perioperative mortality rates. This study investigated the perioperative and postoperative outcomes in ESRD patients receiving propofol target-controlled infusion with brachial plexus block during arteriovenous (AV) access surgery. Materials and Methods: We recruited fifty consecutive patients scheduled to receive AV access surgery. While all patients received general anesthesia combined with ultrasound-guided brachial plexus block, the patients were randomly assigned to one of two general anesthesia maintenance groups, with 23 receiving propofol target-controlled infusion (TCI) and 24 receiving sevoflurane inhalation. We measured perioperative mean arterial pressure (MAP), heart rate, and cardiac output and recorded postoperative pain status and adverse events in both groups. Results: ESRD patients receiving propofol TCI had significantly less reduction in blood pressure than those receiving sevoflurane inhalation (p < 0.05) during AV access surgery. Perioperative cardiac output and heart rate were similar in both groups. Both groups reported relatively low postoperative pain score and a low incidence of adverse events. Conclusions: Propofol TCI with brachial plexus block can be used as an effective anesthesia regimen for ESRD patients receiving AV access surgery. It can be used with less blood pressure fluctuation than inhalational anesthesia.

Negative drift of sedation depth in critically ill patients receiving constant minimum alveolar concentration of isoflurane, sevoflurane, or desflurane: a randomized controlled trial.

BACKGROUND: Intensive care unit (ICU) physicians have extended the minimum alveolar concentration (MAC) to deliver and monitor long-term volatile sedation in critically ill patients. There is limited evidence of MAC's reliability in controlling sedation depth in this setting. We hypothesized that sedation depth, measured by the electroencephalography (EEG)-derived Narcotrend-Index (burst-suppression N_Index 0-awake N_Index 100), might drift downward over time despite constant MAC values. METHODS: This prospective single-centre randomized clinical study was conducted at a University Hospital Surgical Intensive Care Unit and included consecutive, postoperative ICU patients fulfilling the inclusion criteria. Patients were randomly assigned to receive uninterrupted inhalational sedation with isoflurane, sevoflurane, or desflurane. The end-expiratory concentration of the anaesthetics and the EEG-derived index were measured continuously in time-stamped pairs. Sedation depth was also monitored using Richmond-Agitation-Sedation-Scale (RASS). The paired t-test and linear models (bootstrapped or multilevel) have been employed to analyze MAC, N_Index and RASS across the three groups. RESULTS: Thirty patients were recruited (female/male: 10/20, age 64 ± 11, Simplified Acute Physiology Score II 30 ± 10). In the first 24 h, 21.208 pairs of data points (N_Index and MAC) were recorded. The median MAC of 0.58 ± 0.06 remained stable over the sedation time in all three groups. The t-test indicated in the isoflurane and sevoflurane groups a significant drop in RASS and EEG-derived N_Index in the first versus last two sedation hours. We applied a multilevel linear model on the entire longitudinal data, nested per patient, which produced the formula N_Index = 43 - 0.7·h (R2 = 0.76), showing a strong negative correlation between sedation's duration and the N_Index. Bootstrapped linear models applied for each sedation group produced: N_Index of 43-0.9, 45-0.8, and 43-0.4·h for isoflurane, sevoflurane, and desflurane, respectively. The regression coefficient for desflurane was almost half of those for isoflurane and sevoflurane, indicating a less pronounced time-effect in this group. CONCLUSIONS: Maintaining constant MAC does not guarantee stable sedation depth. Thus, the patients necessitate frequent clinical assessments or, when unfeasible, continuous EEG monitoring. The differences across different volatile anaesthetics regarding their time-dependent negative drift requires further exploration. TRIAL REGISTRATION: NCT03860129.

Sevoflurane impedes glioma progression via regulating circ_0000215/miR-1200/NCR3LG1 axis.

Sevoflurane has been reported to have anti-tumorigenic effects in glioma. Circ_0000215 was found to play vital functions in the pathological progressions of glioma. However, whether circ_0000215 mediates the inhibitory effects of sevoflurane on glioma cells remains unclear. In vitro assays were performed using cell counting kit-8, flow cytometry, transwell and Western blot assays. The expression levels of circ_0000215, microRNA (miR)-1200 and NCR3LG1 (Natural Killer Cell Cytotoxicity Receptor 3 Ligand 1) were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and/or Western blot. The dual-luciferase reporter assay and pull-down assay were used to investigate the relationship between miR-1200 and circ_0000215 or NCR3LG1. In vivo assay was conducted using xenograft nude mice model. In vitro assays suggested that sevoflurane repressed glioma cell proliferation, metastasis and induced apoptosis as well as hindered tumor growth in vivo, which were reversed by circ_0000215 overexpression. Mechanically, circ_0000215 was confirmed to directly target miR-1200, and NCR3LG1 was a target of miR-1200 in glioma cells. Importantly, circ_0000215 could regulate NCR3LG1 expression via miR-1200. Besides that, rescue assay suggested that circ_0000215 attenuated the inhibitory effects of sevoflurane on glioma cell growth and metastasis, which were reversed by miR-1200 overexpression or NCR3LG1 knockdown. Our study revealed that sevoflurane could suppress glioma tumorigenesis by regulating circ_0000215/miR-1200/NCR3LG1 axis, suggesting a new insight into the therapeutic potential of sevoflurane in glioma treatment.

Molecular Aspects of Volatile Anesthetic-Induced Organ Protection and Its Potential in Kidney Transplantation.

Ischemia reperfusion injury (IRI) is inevitable in kidney transplantation and negatively impacts graft and patient outcome. Reperfusion takes place in the recipient and most of the injury following ischemia and reperfusion occurs during this reperfusion phase; therefore, the intra-operative period seems an attractive window of opportunity to modulate IRI and improve short- and potentially long-term graft outcome. Commonly used volatile anesthetics such as sevoflurane and isoflurane have been shown to interfere with many of the pathophysiological processes involved in the injurious cascade of IRI. Therefore, volatile anesthetic (VA) agents might be the preferred anesthetics used during the transplantation procedure. This review highlights the molecular and cellular protective points of engagement of VA shown in in vitro studies and in vivo animal experiments, and the potential translation of these results to the clinical setting of kidney transplantation.

Use of topical sevoflurane in pressure ulcer treatment in a double-lung transplant patient.

Pain caused by wounds of different etiology is usually treated with oral analgesics. New topical use of products such as the ether anesthetic sevoflurane shows good results for pain control and has additional benefits. Pressure ulcers are painful and patients may benefit from the use of sevoflurane. We present the case of a double-lung transplant patient with a long-standing sacral pressure ulcer with poor pain control, for which sevoflurane dressings were used. The number of pain-free hours after application, the amount of daily analgesics and the size of the wound were monitored with the mobile wound application MOWA. After several days of sevoflurane application, the patient reduced analgesic consumption, remained longer free of pain, and the size of the wound decreased. Unfortunately, the patient had serious complications due to multiple comorbidities and died before the wound healed completely. Topical use of sevoflurane in pressure ulcers may be a good option to treat pain and improve patient quality of life.

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.