Influencing Factors of Delirium during Recovery in Urological Postoperative Patients Undergoing Sevoflurane Anaesthesia.

OBJECTIVE: To analyse the incidence and influencing factors of delirium during recovery in urological postoperative patients undergoing sevoflurane anaesthesia. METHODS: The clinical data of patients undergoing sevoflurane anaesthesia in the urology surgery department in our hospital from January 2022 to December 2022 were retrospectively analysed. The incidence of delirium during the recovery period was recorded by using the Chinese version of the Confusion Assessment Method (CAM) for Severity of Delirium after surgery, and the patients were divided into occurrence and non-occurrence groups. Whether delirium occurred during recovery was determined through univariate analysis. In binary logistic regression analysis, the occurrence of emergence delirium was the dependent variable, and the variables with statistical differences in the univariate analysis were the independent variables. The influencing factors of emergence delirium in post-urological surgery patients who underwent sevoflurane anaesthesia were determined. RESULTS: Delirium during recovery occurred in 10 of 100 patients (10.00%). Odds ratio (OR) of age (OR = 1.445, p = 0.022), history of diabetes (OR = 1.798, p = 0.010), operation time (OR = 1.670, p = 0.008), American Society of Anesthesiologists (ASA) classification (OR = 1.740, p = 0.006) and sevoflurane inhalation concentration (OR = 1.890, p = 0.001) are the influencing factors of postoperative delirium in urologic patients undergoing sevoflurane anaesthesia. CONCLUSIONS: Age, history of diabetes, operation time, ASA classification and sevoflurane inhalation concentration are the influencing factors.

Involvement of Fgf2-mediated tau protein phosphorylation in cognitive deficits induced by sevoflurane in aged rats.

OBJECTIVE: Anesthetics have been linked to cognitive alterations, particularly in the elderly. The current research delineates how Fibroblast Growth Factor 2 (Fgf2) modulates tau protein phosphorylation, contributing to cognitive impairments in aged rats upon sevoflurane administration. METHODS: Rats aged 3, 12, and 18 months were subjected to a 2.5% sevoflurane exposure to form a neurotoxicity model. Cognitive performance was gauged, and the GEO database was employed to identify differentially expressed genes (DEGs) in the 18-month-old cohort post sevoflurane exposure. Bioinformatics tools, inclusive of STRING and GeneCards, facilitated detailed analysis. Experimental validations, both in vivo and in vitro, examined Fgf2's effect on tau phosphorylation. RESULTS: Sevoflurane notably altered cognitive behavior in older rats. Out of 128 DEGs discerned, Fgf2 stood out as instrumental in regulating tau protein phosphorylation. Sevoflurane exposure spiked Fgf2 expression in cortical neurons, intensifying tau phosphorylation via the PI3K/AKT/Gsk3b trajectory. Diminishing Fgf2 expression correspondingly curtailed tau phosphorylation, neurofibrillary tangles, and enhanced cognitive capacities in aged rats. CONCLUSION: Sevoflurane elicits a surge in Fgf2 expression in aging rats, directing tau protein phosphorylation through the PI3K/AKT/Gsk3b route, instigating cognitive aberrations.

Acute Intraoperative Tympanic Membrane Rupture in Patient Anesthetized With Desflurane Without Nitrous Oxide: A Case Report.

We report a case of acute intraoperative tympanic membrane (TM) rupture in a patient anesthetized with desflurane without N2O. The patient was undergoing endoscopic retrograde cholangiopancreatography (ERCP) to treat ascending cholangitis. TM rupture is known to occur with N2O but has not been reported in the literature with the use of inhaled volatile anesthetics without N2O. We suspect that several factors contributed to this complication, including prone positioning, a remote history of ear trauma, and the selection of desflurane as the maintenance anesthetic as opposed to a vapor with a higher blood-gas partition coefficient.

Dysregulation of iron homeostasis and ferroptosis in sevoflurane and isoflurane associated perioperative neurocognitive disorders.

In recent years, sevoflurane and isoflurane are the most popular anesthetics in general anesthesia for their safe, rapid onset, and well tolerant. Nevertheless, many studies reported their neurotoxicity among pediatric and aged populations. This effect is usually manifested as cognitive impairment such as perioperative neurocognitive disorders. The wide application of sevoflurane and isoflurane during general anesthesia makes their safety a major health concern. Evidence indicates that iron dyshomeostasis and ferroptosis may establish a role in neurotoxicity of sevoflurane and isoflurane. However, the mechanisms of sevoflurane- and isoflurane-induced neuronal injury were not fully understood, which poses a barrier to the treatment of its neurotoxicity. We, therefore, reviewed the current knowledge on mechanisms of iron dyshomeostasis and ferroptosis and aimed to promote a better understanding of their roles in sevoflurane- and isoflurane-induced neurotoxicity.

Evaluation of Quality of Recovery With Quality of Recovery-15 Score After Closed-Loop Anesthesia Delivery System-Guided Propofol Versus Desflurane General Anesthesia in Patients Undergoing Transabdominal Robotic Surgery: A Randomized Controlled Study.

BACKGROUND: Robotic technique of surgery allows surgeons to perform complex procedures in difficult-to-access areas of the abdominal/pelvic cavity (eg, radical prostatectomy and radical hysterectomy) with improved access and precision approach. At the same time, automated techniques efficiently deliver propofol total intravenous anesthesia (TIVA) with lower anesthetic consumption. As both above are likely to bring benefit to the patients, it is imperative to explore their effect on postanesthesia recovery. Quality of Recovery-15 (QoR-15) is a comprehensive patient-reported measure of the quality of postanesthesia recovery and assesses compendious patients' experiences (physical and mental well-being). This randomized study assessed the effect of automated propofol TIVA versus inhaled desflurane anesthesia on postoperative quality of recovery using the QoR-15 questionnaire in patients undergoing elective robotic surgery. METHODS: One hundred twenty patients undergoing robotic abdominal surgery under general anesthesia (GA) were randomly allocated to receive propofol TIVA administered by closed-loop anesthesia delivery system (CLADS) (CLADS group) or desflurane GA (desflurane group). Postoperative QoR-15 score on postoperative day 1 (POD-1) and postoperative day 2 (POD-2) (primary outcome variables), individual QoR-15 item scores (15 nos.), intraoperative hemodynamics (heart rate, mean blood pressure), anesthesia depth consistency, anesthesia delivery system performance, early recovery from anesthesia (time-to-eye-opening, and time to tracheal extubation), and postoperative adverse events (sedation, postoperative nausea and vomiting [PONV], pain, intraoperative awareness recall) (secondary outcome variables) were analyzed. RESULTS: On POD-1, the CLADS group scored significantly higher than the desflurane group in terms of "overall" QoR-15 score (QoR-15 score: 114.5 ± 13 vs 102.1 ± 20.4; P = .001) and 3 individual QoR-15 "items" scores ("feeling rested" 7.5 ± 1.9 vs 6.4 ± 2.2, P = .007; "good sleep" 7.8 ± 1.9 vs 6.6 ± 2.7, P = .027; and "feeling comfortable and in control" 8.1 ± 1.7 vs 6.9 ± 2.4, P = .006). On the POD-2, the CLADS group significantly outscored the desflurane group with respect to the "overall" QoR-15 score (126.0 ± 13.6 vs 116.3 ± 20.3; P = .011) and on "5" individual QoR-15 items ("feeling rested" 8.1 ± 1.4 vs 7.0 ± 2.0, P = .003; "able to return to work or usual home activities" 6.0 ± 2.2 vs 4.6 ± 2.6, P = .008; "feeling comfortable and in control" 8.6 ± 1.2 vs 7.7 ± 1.9, P = .004; "feeling of general well-being" 7.8 ± 1.6 vs 6.9 ± 2.0, P = .042; and "severe pain" 9.0 ± 1.9 vs 8.1 ± 2.5, P = .042). CONCLUSIONS: Automated propofol TIVA administered by CLADS is superior to desflurane inhalation GA with respect to early postoperative recovery as comprehensively assessed on the QoR-15 scoring system. The effect of combined automated precision anesthesia and surgery (robotics) techniques on postoperative recovery may be explored further.

Inhaled methoxyflurane (Penthrox) administration in dentistry as an alternative to nitrous oxide sedation: a review and feasibility study.

Methoxyflurane (MOF) as an agent for dental sedation has been used safely in Australasia for decades. The drug is now licensed for relief of pain associated with trauma and is being used during several medical outpatient procedures in the stead of traditional intravenous agents for sedation in the UK. Our aim was to analyse the safety and feasibility of the introduction of MOF as a drug for dental sedation in the UK community setting and assess its environmental impact. A literature review was conducted for available studies and a research audit of medical histories of patients that received nitrous oxide sedation in the previous year was carried out to assess suitability for MOF administration. The published literature shows MOF to be a safe drug for administration in the dental environment and local patients receiving nitrous oxide sedation are medically suitable for MOF administration. The advantages of considering MOF sedation are its environmental benefit and patient acceptability.

Randomized controlled trial of the effect of general anesthetics on postoperative recovery after minimally invasive nephrectomy.

BACKGROUND: General anesthetic techniques can affect postoperative recovery. We compared the effect of propofol-based total intravenous anesthesia (TIVA) and desflurane anesthesia on postoperative recovery. METHODS: In this randomized trial, 150 patients undergoing robot-assisted or laparoscopic nephrectomy for renal cancer were randomly allocated to either the TIVA or desflurane anesthesia (DES) group. Postoperative recovery was evaluated using the Korean version of the Quality of Recovery-15 questionnaire (QoR-15K) at 24 h, 48 h, and 72 h postoperatively. A generalized estimating equation (GEE) was performed to analyze longitudinal QoR-15K data. Fentanyl consumption, pain severity, postoperative nausea and vomiting, and quality of life three weeks after discharge were also compared. RESULTS: Data were analyzed for 70 patients in each group. The TIVA group showed significantly higher QoR-15K scores at 24 and 48 h postoperatively (24 h: DES, 96 [77, 109] vs. TIVA, 104 [82, 117], median difference 8 [95% CI: 1, 15], P = 0.029; 48 h: 110 [95, 128] vs. 125 [109, 130], median difference 8 [95% CI: 1, 15], P = 0.022), however not at 72 h (P = 0.400). The GEE revealed significant effects of group (adjusted mean difference 6.2, 95% CI: 0.39, 12.1, P = 0.037) and time (P < 0.001) on postoperative QoR-15K scores without group-time interaction (P = 0.051). However, there were no significant differences in other outcomes, except for fentanyl consumption, within the first 24 h postoperatively. CONCLUSIONS: Propofol-based TIVA showed only a transient improvement in postoperative recovery than desflurane anesthesia, without significant differences in other outcomes.

Intravenous MELAtonin for prevention of Postoperative Agitation and Emergence Delirium in children (MELA-PAED): A protocol and statistical analysis plan for a randomized clinical trial.

BACKGROUND: Emergence agitation and delirium in children remain a common clinical challenge in the post-anesthetic care unit. Preoperative oral melatonin has been suggested as an effective preventive drug with a favorable safety profile. The oral bioavailability of melatonin, however, is low. Therefore, the MELA-PAED trial aims to investigate the efficacy and safety of intraoperative intravenous melatonin for the prevention of emergence agitation in pediatric surgical patients. METHODS: MELA-PAED is a randomized, double-blind, parallel two-arm, multi-center, superiority trial comparing intravenous melatonin with placebo. Four hundred participants aged 1-6 years will be randomized 1:1 to either the intervention or placebo. The intervention consists of intravenous melatonin 0.15 mg/kg administered approximately 30 min before the end of surgery. Participants will be monitored in the post-anesthetic care unit (PACU), and the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery (PHBQ-AS) will be performed on days 1, 7, and 14 after the intervention. Serious Adverse Events (SAE) will be assessed up to 30 days after the intervention. RESULTS: The primary outcome is the incidence of emergence agitation, assessed dichotomously as any Watcha score >2 during the participant's stay in the post-anesthetic care unit. Secondary outcomes are opioid consumption in the post-anesthetic care unit and adverse events. Exploratory outcomes include SAEs, postoperative pain, postoperative nausea and vomiting, and time to awakening, to first oral intake, and to discharge readiness. CONCLUSION: The MELA-PAED trial investigates the efficacy of intravenous intraoperative melatonin for the prevention of emergence agitation in pediatric surgical patients. Results may provide further knowledge concerning the use of melatonin in pediatric perioperative care.

Comparison of Volatile Anesthetics Versus Propofol on Postoperative Cognitive Function After Cardiac Surgery: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare the effects of volatile anesthetics and propofol on neurocognitive function after cardiac surgery. DESIGN: A systematic review and meta-analysis of randomized controlled trials. SETTING: A literature search of PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and Web of Science databases was conducted. PARTICIPANTS: A total of 10 randomized controlled trials comparing volatile anesthetics and propofol in cardiac surgery were included in the study. INTERVENTIONS: The standardized mean difference and risk ratio were calculated to estimate pooled effect sizes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the postoperative neurocognitive function score, and the secondary outcome was the incidence of delirium after cardiac surgery. The analysis did not show significant differences in postoperative neurocognitive function scores (standardized mean difference -0.06, 95% CI -0.81-0.69; p = 0.879). The incidences of delirium (risk ratio 1.10, 95% CI 0.81-1.50) between the volatile anesthetics and propofol groups were not significant (p = 0.533). CONCLUSIONS: Unlike noncardiac surgery, there are no differences between volatile anesthetics and propofol regarding postoperative neurocognitive dysfunction after cardiac surgery.

A randomized controlled trial of propofol-remifentanil total intravenous anesthesia and sevoflurane-fentanyl anesthesia on early postoperative fatigue in patients undergoing laparoscopic colorectal surgery.

PURPOSE: Even after uncomplicated surgery, postoperative fatigue prevalence has been reported to be 30-80% for various surgeries. We evaluated postoperative fatigue according to anesthetic technique in patients who underwent colorectal surgery. METHODS: One hundred thirty patients who underwent colorectal surgery were randomly assigned to either propofol-remifentanil total intravenous anesthesia (propofol-remifentanil group, n = 65) or sevoflurane-fentanyl anesthesia (sevoflurane-fentanyl group, n = 65). The primary outcome was the prevalence of postoperative fatigue, as defined by the Chalder Fatigue Questionnaire (total score ≥ 16), at 24 h postoperatively. Secondary outcomes were early postoperative complications during hospitalization and laboratory examination. RESULTS: The final analyses included 127 patients. The prevalence of postoperative fatigue on the 1st postoperative day was lower in the propofol-remifentanil group than the sevoflurane-fentanyl group: 56.3% (36/64) in the propofol-remifentanil group and 73.0% (46/63) in the sevoflurane-fentanyl group (relative risk [RR] = 0.77, 95% confidence interval [CI] 0.59-1.00; P = 0.048). However, there was no difference between the two groups in postoperative fatigue at postoperative day 3. Other postoperative outcomes including the severity of pain and the incidence of nausea/vomiting were not different between the two groups, but postoperative atelectasis on chest X-ray was higher in the sevoflurane-fentanyl group (2/64 [3.1%] vs. 9/63 [14.3%], P = 0.025). C-reactive protein change from preoperative to postoperative day 1 and 5 was significantly lower in the propofol-remifentanil group (P = 0.044). CONCLUSION: Propofol-remifentanil total intravenous anesthesia was associated with reduced postoperative fatigue at the 1st postoperative day compared with sevoflurane-fentanyl anesthesia. Clinical trial The Korean Clinical Research Registry (study identifier: KCT0006917, principal investigator's name: MiHye Park, date of registration: January 12, 2022).

Incidence of emergence agitation in children undergoing sevoflurane anesthesia compared to isoflurane anesthesia: An updated systematic review and meta-analysis.

BACKGROUND: Emergence agitation is a complex syndrome of altered consciousness after emergence from anesthesia. It can result in injury to patients and staff and is associated with other postoperative complications. Sevoflurane has been associated with emergence agitation, potentially due to low tissue solubility and therefore speed of emergence. Prior meta-analyses comparing emergence agitation incidence between sevoflurane and isoflurane anesthetics did not demonstrate a statistically significant difference. Given the publication of additional relevant studies not included in prior meta-analyses as well as improved diagnosis of emergence agitation, we aim to perform an updated, comprehensive meta-analysis comparing emergence agitation incidence between sevoflurane and isoflurane anesthetics in children. METHODS: We conducted an updated systematic review and meta-analysis of clinical trials comparing sevoflurane to isoflurane in children <18 years of age, reporting emergence agitation as an outcome, published before July 2023 using databases and registers. Our primary outcome was the incidence of emergence agitation. Secondary outcomes were time to extubation, awakening time, and length of stay in the postanesthetic care unit. We assessed the risk of bias using the Cochrane Risk of Bias tool version 2. We pooled the effect size for the outcomes using the fixed effects model if we had low heterogeneity, otherwise, we used a random-effects model. RESULTS: Eight randomized controlled trials (523 children) were included in the final analysis. The incidence of emergence agitation after isoflurane was significantly lower compared to sevoflurane (risk ratio: 0.62 (95% CI: [0.46-0.83]; I2 = 40.01%, p < .001)). Time to extubation, awakening times, and postanesthetic care unit duration were not significantly different. The protective effect of isoflurane compared to sevoflurane remained significant in subgroups of patients who received premedication or intraoperative systemic analgesics (risk ratios: (0.48 [0.28-0.82]; I2 = 60.78%, p = .01), (0.52 [0.37-0.75]; I2 = 0.00%, p < .001), respectively). CONCLUSION: The risk of emergence agitation in children after maintenance anesthesia with sevoflurane is significantly greater than with isoflurane; we did not find evidence of prolonged emergence or postanesthetic length of stay. When possible, isoflurane should be considered for maintenance anesthesia over sevoflurane in patients at high risk of emergence agitation.

Differential effects of sevoflurane and desflurane on frontal intraoperative electroencephalogram dynamics associated with postoperative delirium.

STUDY OBJECTIVE: Intraoperative electroencephalogram (EEG) patterns associated with postoperative delirium (POD) development have been studied, but the differences in EEG recordings between sevoflurane- and desflurane-induced anesthesia have not been clarified. We aimed to distinguish the EEG characteristics of sevoflurane and desflurane in relation to POD development. DESIGN AND PATIENTS: We collected frontal four-channel EEG data during the maintenance of anesthesia from 148 elderly patients who received sevoflurane (n = 77) or desflurane (n = 71); 30 patients were diagnosed with delirium postoperatively. The patients were divided into four subgroups based on anesthetics and delirium status: sevoflurane delirium (n = 17), sevoflurane non-delirium (n = 60), desflurane delirium (n = 13), and desflurane non-delirium (n = 58). We compared spectral power, coherence, and pairwise phase consistency (PPC) between sevoflurane and desflurane, and between non-delirium and delirium groups for each anesthetic. MAIN RESULTS: In patients without POD, the sevoflurane non-delirium group exhibited higher EEG spectral power across 8.5-35 Hz (99.5% CI bootstrap analysis) and higher PPC from alpha to gamma bands (p < 0.005) compared to the desflurane non-delirium group. Conversely, in patients with POD, no significant EEG differences were observed between the sevoflurane and desflurane delirium groups. For the sevoflurane-induced patients, the sevoflurane delirium group had significantly lower power within 7.5-31.5 Hz (99.5% CI bootstrap analysis), reduced coherence over 8.9-23.8 Hz (99.5% CI bootstrap analysis), and lower PPC values in the alpha band (p < 0.005) compared with the sevoflurane non-delirium group. For the desflurane-induced patients, there were no significant differences in the EEG patterns between delirium and non-delirium groups. CONCLUSIONS: In normal patients without POD, sevoflurane demonstrates a higher power spectrum and prefrontal connectivity than desflurane. Furthermore, reduced frontal alpha power, coherence, and connectivity of intraoperative EEG could be associated with an increased risk of POD. These intraoperative EEG characteristics associated with POD are more noticeable in sevoflurane-induced anesthesia than in desflurane-induced anesthesia.

Effect of nitrous oxide on clinical outcome in patients undergoing cerebellopontine tumor surgery under sevoflurane anesthesia: a randomized controlled trial.

Nitrous oxide (N2O) is a unique anesthetic agent that has both advantages and disadvantages, especially in neurosurgical patients. Various studies evaluating the use of N2O in different surgical populations have been inconclusive so far. In this prospective, single-blinded, randomized study, 50 patients of either sex, aged 18-60 years, were enrolled and randomly allocated into N2O or N2O free group. Data including demographics, intraoperative vitals, blood gases, intravenous fluids, anesthetic drug consumption, brain condition, emergence and recovery time, duration of surgery and anesthesia, duration of postoperative ventilation, perioperative complications, condition at discharge, and duration of intensive care unit & hospital stay were recorded. There was no significant difference in intensive care unit or hospital stay between the groups. However, a significant difference in intraoperative heart rate and mean arterial pressure was observed. The incidence of intraoperative tachycardia and hypotension was significantly higher in the N2O free group. Other intra- and post-operative parameters, perioperative complications, and conditions at discharge were comparable. Use of N2O anesthesia for cerebellopontine tumor surgery in good physical grade and well-optimized patients neither increases the length of intensive care unit or hospital stay nor does it affect the complications and conditions at discharge. However, future studies in poor-grade patients with large tumors and raised intracranial pressure will be required to draw a definitive conclusion.

Neuroprotective potential of sevoflurane against isoflurane induced cognitive dysfunction in rats via anti-inflammatory and antioxidant effect.

PURPOSE: Intravenous anesthetics have excellent analgesic activity without inducing the side effect in the respiratory system. The aim and objective of the current experimental study was to access the neuroprotective effect of sevoflurane against isoflurane induced cognitive dysfunction in rats. METHODS: Isoflurane was used for induction the neurodysfunction in the rats, and rats received the oral administration of sevoflurane (2.5, 5 and 10 mg/kg). Morris water test was carried out for the estimation of cognitive function. Neurochemical parameters, antioxidant parameters and pro-inflammatory cytokines were also estimated. RESULTS: Sevoflurane significantly (P < 0.001) altered the neurochemical parameters such as anti-choline acetyltransferase, acetylcholine esterase, acetylcholine, protein carbonyl, choline brain-derived neurotrophic factor, and amyloid ß; antioxidant parameters such as glutathione, superoxide dismutase, and malondialdehyde; pro-inflammatory cytokines include interleukin (IL-2, IL-10, IL-4, IL-6, IL-10, IL-1ß), and tumor necrosis factor-α. Sevoflurane significantly reduced the activity of caspase-3. CONCLUSIONS: Sevoflurane exhibited the neuroprotection against the cognitive dysfunction in rats via anti-inflammatory and antioxidant mechanism.

Protocol for a randomized controlled trial to reduce pediatric anesthesia emergence delirium by titration of sevoflurane anesthesia using brain function monitoring.

BACKGROUND: Emergence agitation or emergence delirium is a common complication of unknown etiology in pediatric anesthesia. Pediatric anesthesia emergence delirium (PAED) has been reported most commonly in younger children and may occur in about 30% of children up to 5-6 years old. Exposure to anesthetic agents may contribute to PAED, and we hypothesized that a management strategy to minimize exposure to volatile anesthetics may reduce PAED. Electroencephalography (EEG) signatures captured and displayed by brain function monitors during anesthesia change with concentration of sevoflurane and level of unconsciousness, and these EEG signatures may be used to inform titration of anesthetics. METHODS: A single-center, parallel-group, two-arm, superiority trial with a 1:1 allocation ratio will be performed to compare the incidence of PAED following standard sevoflurane anesthesia (maintained at 1.0MAC) and EEG-guided anesthesia (minimum concentration to sustain surgical anesthesia as determined by monitoring of EEG signatures). Participants between 1 and 6 years of age undergoing surgical procedures involving minimal postoperative pain will be randomly assigned to receive standard (n = 90) or EEG-guided (n = 90) anesthesia. PAED score will be assessed by a blinded observer in the PACU on arrival and after 5, 10, 15, and 30 min. DISCUSSION: Anesthesia management with proactive use of brain function monitoring is expected to reduce exposure to sevoflurane without compromising surgical anesthesia. We expect this reduced exposure should help prevent PAED. Routinely administering what may be considered standard levels of anesthetic such as 1.0 MAC sevoflurane may be excessive and potentially associated with unfavorable sequelae such as PAED. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) jRCTs032210248. Prospectively registered on 17 August 2021.

Sucking lollipop after awakening from sevoflurane anesthesia reduces the degree of emergence agitation in children undergoing ambulatory surgery: A prospective randomized controlled trial.

BACKGROUND: Emergence agitation (EA) is a common complication in pediatric anesthesia, especially in preschool children maintained by sevoflurane, with incidence ranging up to 80%. The purpose of the study was to determine whether sucking lollipop after awakening from sevoflurane anesthesia reduced the degree of EA in children undergoing ambulatory surgery. METHODS: In this prospective study, 40 children aged 2 to 6 years scheduled for ambulatory surgery with sevoflurane were enrolled. They were randomly allocated to 1 of 2 groups after evaluating baseline EA levels using the pediatric anesthesia emergence delirium (PAED) scale immediately after awakening from general anesthesia: group L (sucking lollipop) or group C (control group, without sucking lollipop). The primary outcome was the overall PAED score after intervention. Pain score, parental satisfaction, the incidence of propofol rescue and negative postoperative behavioral changes (NPOBCs) were assessed. RESULTS: The overall PAED score after intervention was significantly lower in Group L compared with Group C, with an estimated difference of -1.857 (95% CI, -2.884 to -0.831; P < .001) using generalized estimating equations. However, no significant intergroup differences were observed in the pain score, parental satisfaction, the incidence of propofol rescue and NPOBCs. CONCLUSIONS: Sucking lollipop after awakening from sevoflurane anesthesia reduced the degree EA in children undergoing ambulatory surgery.

Immunomodulatory and pro-oncologic effects of ketamine and isoflurane anesthetics in a murine model.

INTRODUCTION: Volatile and intravenous anesthetics may worsen oncologic outcomes in basic science animal models. These effects may be related to suppressed innate and adaptive immunity, decreased immunosurveillance, and disrupted cellular signaling. We hypothesized that anesthetics would promote lung tumor growth via altered immune function in a murine model and tested this using an immunological control group of immunodeficient mice. METHODS: Lewis lung carcinoma cells were injected via tail vein into C57BL/6 immunocompetent and NSG immunodeficient mice during exposure to isoflurane and ketamine versus controls without anesthesia. Mice were imaged on days 0, 3, 10, and 14 post-tumor cell injection. On day 14, mice were euthanized and organs fixed for metastasis quantification and immunohistochemistry staining. We compared growth of tumors measured from bioluminescent imaging and tumor metastasis in ex vivo bioluminescent imaging of lung and liver. RESULTS: Metastases were significantly greater for immunocompromised NSG mice than immunocompetent C57BL/6 mice over the 14-day experiment (partial η2 = 0.67, 95% CI = 0.54, 0.76). Among immunocompetent mice, metastases were greatest for mice receiving ketamine, intermediate for those receiving isoflurane, and least for control mice (partial η2 = 0.88, 95% CI = 0.82, 0.91). In immunocompetent mice, significantly decreased T lymphocyte (partial η2 = 0.83, 95% CI = 0.29, 0.93) and monocyte (partial η2 = 0.90, 95% CI = 0.52, 0.96) infiltration was observed in anesthetic-treated mice versus controls. CONCLUSIONS: The immune system appears central to the pro-metastatic effects of isoflurane and ketamine in a murine model, with decreased T lymphocytes and monocytes likely playing a role.

Real world safety of methoxyflurane analgesia in the emergency setting: a comparative hybrid prospective-retrospective post-authorisation safety study.

BACKGROUND: Low-dose analgesic methoxyflurane (Penthrox®) was approved in Europe for emergency relief of moderate to severe pain in conscious adults with trauma in 2015. A comparative post-authorisation safety study (PASS) was conducted to assess the risk of hepatotoxicity and nephrotoxicity with methoxyflurane during routine clinical practice. METHODS: This was a comparative hybrid prospective-retrospective cohort study. The comparative cohorts consisted of adults who were given methoxyflurane (methoxyflurane cohort) or another analgesic (concurrent cohort) routinely used for moderate to severe trauma and associated pain in the emergency setting (ambulance and Emergency Department) in the UK between December 2016 and November 2018. Hepatic and renal events were captured in the ensuing 12 weeks. A blinded clinical adjudication committee assessed events. A historical comparator cohort (non-concurrent cohort) was identified from patients with fractures in the English Hospital Episode Statistics (HES) accident and emergency database from November 2013 and November 2015 (before commercial launch of methoxyflurane). Hepatic and renal events were captured in the ensuing 12 weeks via linkage with the Clinical Practice Research Datalink (CPRD) and HES hospital admissions databases. RESULTS: Overall, 1,236, 1,101 and 45,112 patients were analysed in the methoxyflurane, concurrent and non-concurrent comparator cohorts respectively. There was no significant difference in hepatic events between the methoxyflurane and concurrent cohorts (1.9% vs. 3.0%, P = 0.079) or between the methoxyflurane and non-concurrent cohorts (1.9% vs. 2.5%, P = 0.192). Renal events were significantly less common in the methoxyflurane cohort than in the concurrent cohort (2.3% vs. 5.6%, P < 0.001). For methoxyflurane versus non-concurrent cohort the lower occurrence of renal events (2.3% vs. 3.2%, P = 0.070) was not statistically significant. Multivariable adjustment did not change these associations. CONCLUSIONS: Methoxyflurane administration was not associated with an increased risk of hepatotoxicity or nephrotoxicity compared with other routinely administered analgesics and was associated with a reduced risk of nephrotoxicity compared with other routinely administered analgesics. TRIAL REGISTRATION: Study registered in the EU PAS Register (ENCEPP/SDPP/13040).