Outcomes in patients who received ECMO and/or volatile anesthetics as rescue therapies for status asthmaticus☠.

BACKGROUND: In the state of Kentucky, many status asthmaticus (SA) patients require care in the Pediatric Intensive Care Unit (PICU) and a fraction of these patients may receive "rescue therapies" with inhaled volatile anesthetics (IVA) and/or Extracorporeal Membrane Oxygenation (ECMO). We present a series of such patients with the objective of comparing the clinical parameters of individual patients who received inhaled volatile anesthesia and subsequently the need for ECMO. METHODS: Children between 2 and 18 years of age admitted to our PICU from January 2014 to July 2020 with SA were reviewed and categorized as 1) patients who received IVA alone, 2) patients who received IVA and then subsequently ECMO, and 3) patients on ECMO alone. RESULTS: A total of 1772 children with SA episodes were identified with a mortality of 13 patients. Seven children with SA were identified who received either IVA, ECMO, or both. One patient received only IVA, 5 received both IVA and ECMO and one received only ECMO. All received standard asthma therapies of steroids, albuterol, magnesium sulphate, and aminophylline prior to escalation. Six out of seven refractory SA received IVA, and five (83%) of those were subsequently escalated to ECMO. There was an improvement in mean pH after cannulation compared to IVA. pCO2 levels had no improvement after IVA administration but decreased by an average of 20 points after ECMO. Patients peak inspiratory pressures decreased within the 1st 24 h of ECMO cannulation from a mean of 30 to 18. There were no other complications related to ECMO placement. CONCLUSION: While we cannot decisively draw any conclusions from our study due to the small sample, it was noted that there was no clear advantage of using IVA prior to ECMO in our patients. Most patients who received IVA were escalated to ECMO indicating that early ECMO cannulation may be beneficial. Given the high cost and potential complications of both, there is a need for the development of well-defined guidelines for severe SA management in the PICU.

Sevoflurane: an opportunity for stroke treatment.

In developed countries, stroke is the leading cause of death and disability that affects long-term quality of life and its incidence is increasing. The incidence of ischemic stroke is much higher than that of hemorrhagic stroke. Ischemic stroke often leads to very serious neurological sequelae, which severely reduces the patients' quality of life and becomes a social burden. Therefore, ischemic stroke has received increasing attention. As a new type of anesthetic, sevoflurane has a lower solubility, works faster in the human body, and has less impact on the cardiovascular system than isoflurane. At the same time, studies have shown that preconditioning and postconditioning with sevoflurane have a beneficial effect on stroke. We believe that the role of sevoflurane in stroke may be a key area for future research. Therefore, this review mainly summarizes the relevant mechanisms of sevoflurane preconditioning and postconditioning in stroke in the past 20 years, revealing the bright prospects of sevoflurane in stroke treatment.

The Role of Nitrous Oxide in Minor Pediatric Procedures in the Emergency Department: A Systematic Review.

BACKGROUND: Pediatric patients undergoing minor, but painful procedures in an Emergency Department (ED) need adequate relief of pain and distress to prevent long term negative effects and adversely impact procedures. Inhaled nitrous oxide (N2O) is a needle-free pain management option. We conducted a systematic review to determine whether N2O is as effective as local anesthesia in minor procedures. The purpose of this study was to evaluate available evidence regarding analgesic effectiveness of N2O in pediatric patients. METHODS: We searched MEDLINE, Embase, Cochrane and Cinahl databases for controlled trials published in English with pediatric patients in an ED treated with N2O compared to local anesthesia and with pain as primary outcome. Adverse events was one of the secondary outcomes. The GRADE system was used to rate the overall quality of evidence. RESULTS: We included seven studies with a total of 371 patients. Two studies showed N2O was equally effective in pain treatment as local anesthesia. Five studies showed N2O combined with local anesthesia is more effective in reducing pain than local anesthesia alone. None of the included studies reported major adverse effects. The quality of evidence is low. CONCLUSIONS: N2O can have an important contribution in pain management, but should be combined with local anesthesia for optimal pain management in pediatric patients undergoing minor, but painful procedures in an ED. LEVEL OF EVIDENCE: IV.

Effect of Sevoflurane on the Deep Neuromuscular Blockade in Obese Patients Undergoing Laparoscopic Sleeve Gastrectomy: A Single Center Prospective Randomized Controlled Study.

Objective: Our study aimed to demonstrate that the combination of sevoflurane inhalation with continuous intravenous anesthesia can effectively reduce the dosage of muscle relaxants, shorten extubation time under anesthesia while meeting the requirements of laparoscopic deep neuromuscular block (dNMB) in obese patients. Additionally, we sought to assess the potential reduction in postoperative residual muscle relaxants. Methods: Fifty-nine patients were randomly assigned. Anesthesia-related variables, such as anesthetics dosages, muscle relaxant effective time, clinical muscle relaxant time, muscle relaxant in vivo action time, muscle relaxant recovery time, body movement times, and extubation duration were recorded. Surgery-related variables (the Leiden-Surgical Rating Scale (L-SRS), duration of the procedure) were recorded. Pain was measured using the visual analog scale (VAS) score before leaving the PACU. The duration of the PACU stay and patients' satisfaction levels in the PACU were also recorded. Results: Patients who inhaled sevoflurane during the operation required a lower dosage of muscle relaxant to achieve the same deep neuromuscular block (dNMB) effect. The time from stopping the rocuronium pump to T1 recovery of 90% was shorter, and the time for T1 to recover from 25% to 75% was faster among patients who inhaled sevoflurane during the operation. Furthermore, the sevoflurane combined with continuous intravenous anesthesia group exhibited a shorter extubation time for obese patients undergoing laparoscopic bariatric surgery, along with a reduced risk of experiencing hypoxemia and a shorter observation time in the PACU. Conclusion: Inhaling sevoflurane combined with continuous intravenous anesthesia during the operation effectively reduces the dosage of muscle relaxant required to achieve the same deep neuromuscular block (dNMB) effect. Additionally, this approach significantly shortens the extubation time for obese patients undergoing laparoscopic bariatric surgery and reduces the risk of experiencing hypoxemia, along with reducing the observation time in the PACU.

PREVENTION OF PATHOLOGICAL EFFECT OF ISCHEMIA-REPERFUSION IN LIVER RESECTION BY SEVOFLURANE PRECONDITIONING.

BACKGROUND: The intermittent Pringle maneuver remains the major technique for controlling hemorrhage during liver surgery. Nevertheless, this procedure involves a risk of triggering a cascade of pathological changes resulting in the ischemia-reperfusion injury (I/R) effect. The pharmacological prevention of this I/R injury represents a promising approach. The aim of the study was to compare the effects of pharmacological preconditioning with sevoflurane and propofol-based intravenous anesthesia on the postoperative function of the liver as the primary end-point. MATERIALS AND METHODS: A prospective cohort study includes the analysis of the data of 73 patients who underwent liver surgery. In the study group (n = 41), preconditioning with sevoflurane inhalation was provided 30 minutes prior to liver resection. In the control group (n = 32), sevoflurane preconditioning was not provided. The primary endpoints were blood lactate concentration shortly after the surgery and one day later; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities on postoperative Days 1, 3, and 5 as markers of hepatocyte damage. RESULTS: On postoperative Day 1, in patients of the study group, lactate decreased to preoperative levels, while in the control group, lactate content increased as compared to both preoperative levels and the levels immediately after liver resection. A significant difference in AST activity levels between the groups was registered on Day 5, although this difference was not clinically relevant. The decrease in the prothrombin index in the study group on Day 3 was superior to that in the control group. The multiple regression analysis demonstrated a moderate positive association between the number of resected liver segments and the markers of the functional state of the liver in the study group while in the control group, such association was not significant. CONCLUSION: The protective effect of sevoflurane on the postoperative function of the liver is manifested by the lower level of blood lactate and the stable level of transaminase activity.

Propofol suppresses hormones levels more obviously than sevoflurane in pediatric patients with craniopharyngioma: A prospective randomized controlled clinical trial.

OBJECTIVE: General anesthesia can disturb the hormone levels in surgical patients. Hormone deficiency is one of the major symptoms of craniopharyngioma (CP) in pediatric patients. The aim of this prospective randomized controlled clinical study is to evaluate whether propofol and sevoflurane influence the perioperative hormone levels in these patients and to determine which anesthesia technique causes less impact on hormone levels. MATERIALS: Sixty-four ASA I and II pediatric patients with CP undergoing elective neurosurgery were randomly divided into the sevoflurane group (S group, n = 32) and the propofol group (P group, n = 32). Anesthesia was maintained with sevoflurane and propofol until the end of the operation. Demographic information, operation information and hemodynamic variables were recorded. The levels of hormones were evaluated preoperatively as the baseline (T0), 1h after the beginning of the operation (T1), immediately at the end of the operation (T2) and 72 h postoperatively (T3). RESULTS: There were no significant differences in the two groups in terms of patients' demographics and intraoperative information, such as operation duration, blood loss and transfusion volumes, and fluid infusion volume (P>0.05). In both groups, compared to those at T0, the levels of TSH, FT3, TT3 and ACTH at T1, T2 and T3 were significantly lower. The levels of FSH, PRL and GH at T3 were also significantly lower (P<0.05). The FT3 and TT3 levels of both groups at T2 and T3 were significantly lower than those at T1, but the ACTH level was significantly increased (P<0.05). Compared to the levels at T2, the TSH, FT3, FT4 and ACTH levels of the two groups at T3 were significantly reduced (P<0.05). The baseline hormone levels of both groups were similar (P>0.05). At T1, the FT3, TT3, FT4, TT4 and ACTH levels in the P group were significantly lower than those in the S group (P<0.05). At T2, the TT3 and ACTH levels of the P group were significantly lower than those of the S group (P<0.05) At T3, the TT4 level in the P group was significantly lower than that of the S group (P<0.05). CONCLUSION: Propofol and sevoflurane could reduce the levels of hormones intraoperatively and postoperatively in pediatric patients with craniopharyngioma. However, propofol reduced hormone levels more intensively, mainly intraoperatively. Postoperatively, propofol and sevoflurane had similar inhibition effects on the shift in hormone levels. Therefore, in pediatric patients with craniopharyngioma undergoing neurosurgery, sevoflurane might be the preferred anesthetic because it causes less interruption of hormone levels. However, because of their similar postoperative effects, which long-term effects of sevoflurane or propofol could produce optimal clinical situations? Thus more extensive clinical studies are needed. TRIAL REGISTRATION: Clinical trial registration. This trail was registered at Chinese Clinical Trial Registry (http://www.chictr.org.cn, Jun Xiong) on 28/12/2021, registration number was ChiCTR2100054885.

Pain Self-Management with Inhaled Methoxyflurane by Emergency Department Trauma Patients: A Prospective, Interventional, Single-Center Study.

The coronavirus disease 2019 (COVID-19) pandemic has led to overcrowding in many emergency departments (EDs). The present single-center, prospective, interventional study (conducted at Bichat University Medical Center (Paris, France)) was designed to assess the impact of self-administered, inhaled, low-dose methoxyflurane on trauma pain in a pre-ED fast-track zone dedicated to the management of lower-acuity non-COVID-19 patients. In the first phase of the study, the control group consisted of patients with mild-to-moderate trauma pain, for whom the triage nurse initiated pain management (based on the World Health Organization (WHO)'s analgesic ladder). In the second phase, the intervention group consisted of similar patients who self-administered methoxyflurane as an adjuvant to the standard analgesic ladder. The primary endpoint was the numerical pain rating scale (NPRS) score (from 0 to 10) recorded at different time points during the patient's care (T0: arrival in the ED, T1: exit from the triage box, T2: in the radiology department, T3: clinical examination, and T4: discharge from the ED). The level of agreement between the NPRS and the WHO analgesic ladder was assessed by the calculation of Cohen's kappa. Pairwise comparisons of continuous variables were performed with Student's t-test or a non-parametric Mann-Whitney U test. Changes over time in the NPRS were analyzed in an analysis of variance (with Scheffe's post hoc test if a pairwise comparison was significant) or a non-parametric Kruskal-Wallis H test. In all, 268 and 252 patients were included in the control and intervention groups, respectively. The two groups had similar characteristics. The level of agreement between the NPRS score and the analgesic ladder was high in both the control and intervention groups (Cohen's kappa: 0.74 and 0.70, respectively). The NPRS score decreased significantly between T0 and T4 in both groups (p < 0.001), but the decrease between T2 and T4 was significantly greater in the intervention group (p < 0.001). The proportion of patients still in pain on discharge was significantly lower in the intervention group than in the control group (p = 0.001). In conclusion, a combination of self-administered methoxyflurane and the WHO analgesic ladder improves pain management in the ED.

Effects of Pharmacological Intervention on Recovery After Sevoflurane Anesthesia in Children: a Network Meta-analysis of Randomized Controlled Trials.

Sevoflurane, commonly administered to children as anesthesia, often leads to emergence delirium (ED). Currently, a consensus is lacking among clinicians regarding pharmacological interventions to improve recovery. To determine an effective approach, we compared the effects of several drugs in lowering the incidence of ED after sevoflurane anesthesia in children.We searched online databases for relevant randomized controlled trials (59 studies selected; 5199 NMA-eligible participants) and performed a frequentist network meta-analysis (NMA). This study was registered on PROSPERO (number CRD: 42022329939).All included studies had a low to moderate risk of overall bias. The incidence of ED after sevoflurane anesthesia in children differed according to other drugs administered, and were ranked from high to low according to the surface under the cumulative ranking curve (SUCRA).Sufentanil (91.2%) and dexmedetomidine (77.6%) were more likely to reduce the incidence (SUCRA value) of ED, whereas the placebo (6.5%), ramelteon (11.1%), and magnesium (18%) were less likely to reduce the incidence of ED. Remifentanil (89.3%) ranked first in shortening emergence time, followed by placebo (82.4%) and ketamine (69.7%). Placebo shortened extubation time, followed by remifentanil (66.5%) and alfentanil (61.4%).Sufentanil and remifentanil lowered sevoflurane-induced ED incidences among children and shortened the emergence time more effectively than other drugs. Most adjuvant drugs that are combined with sevoflurane either do not change or may even prolong extubation time. Further research and clinical trials are required to support and update these conclusions.

Low-dose epidural anesthesia decreases the use of intraoperative systemic analgesics in goats undergoing lower urinary tract surgery.

OBJECTIVE: To test whether the use of low-dose epidural anesthesia (EA) in goats undergoing lower urinary tract surgery reduces the requirements of perioperative analgesics, contributes to intraoperative hypotension, and improves postoperative comfort during the first 24 hours after surgery. ANIMALS: Retrospective analysis of 38 goats between January 2019 and July 2022. PROCEDURES: Goats were divided into 2 groups (EA or no EA). Demographic characteristics, surgical procedure, time of anesthesia, and anesthetic agents used were compared between treatment groups. Outcome variables potentially related to the use of EA included dose of inhalational anesthetics, incidence of hypotension (mean arterial pressure < 60 mm Hg), intraoperative and postoperative administration of morphine, and time to first meal after surgery. RESULTS: EA (n = 21) consisted of bupivacaine or ropivacaine 0.1% to 0.2% with an opioid. There were no differences between groups except for age (EA group was younger). Less inhalational anesthetic (P = .03) and less intraoperative morphine (P = .008) were used in the EA group. The incidence of hypotension was 52% for EA and 58% for no EA (P = .691). Administration of postoperative morphine was not different between groups (EA, 67%, and no EA, 53%; P = .686). Time to first meal was 7.5 hours (3 to 18 hours) for EA and 11 hours (2 to 24 hours) for no EA (P = .057). CLINICAL RELEVANCE: Low-dose EA reduced the use of intraoperative anesthetics/analgesics in goats undergoing lower urinary tract surgery without an increased incidence of hypotension. Postoperative morphine administration was not reduced.

Literature review on the use of methoxyflurane in the management of pain in cancer-related procedures.

INTRODUCTION: Self-administered methoxyflurane, also known as Penthrox, at a sub-anesthetic dose is a short-term, fast-acting, and safe analgesic that may provide suitable pain relief for cancer patients. This review aims to compile the existing evidence on methoxyflurane and its efficacy in reducing pain during cancer-related procedures. METHODS: A literature search was conducted through OVID Medline and Embase. The search was limited to articles published between 2012 and 2021 and studies were included if they assessed the efficacy of methoxyflurane to reduce pain in cancer-related procedures. All types of cancer were included. RESULTS: The literature search yielded seven studies published between 2012 and 2021. The studies analyzed assessed methoxyflurane use in prostate biopsy, colonoscopy, removal of brachytherapy rods, and bone marrow biopsy. Various research designs were employed, including three randomized controlled trials, two prospective observational studies, one retrospective, and one non-randomized controlled trial. In all, methoxyflurane has a demonstrated ability to reduce pain in these procedures. CONCLUSION: In the limited studies available in evaluating the efficacy of methoxyflurane for reducing procedural pain during cancer-related procedures, all have demonstrated clinical equivalency or superiority. Pain relief appears to be equivalent however methoxyflurane overcomes the standard limitations of respiratory sedation and has demonstrated quicker procedural recovery times than traditional sedation methods. The accumulated data to date supports the use of methoxyflurane which can supplement or supplant current methods of analgesia in cancer-related procedures.

How I Do It: Penthrox in Urology.

Penthrox is a portable handheld inhaler that delivers a low dose of methoxyflurane - an anesthetic with analgesic effects, rapid onset of action, and a favorable side-effect profile. It has been widely used for acute pain management in Australia for the past 40 years. Currently, it is approved for use in over 55 countries, including Canada. Prospective randomized studies highlight Penthrox analgesic effectiveness and safety profile for emergency, prehospital and outpatient settings. In addition, the use of multimodal analgesia, specifically Penthrox, can play an important role in the analgesic management of urological procedures, such as prostatic biopsies and office-based minimally invasive surgical therapies. Herein readers will familiarize themselves with Penthrox, significant studies, and technique used for outpatient urological procedures.

Preventing postoperative cognitive dysfunction using anesthetic drugs in elderly patients undergoing noncardiac surgery: a systematic review and meta-analysis.

Postoperative cognitive dysfunction (POCD) is a common neurological system disorder in surgical patients. The choice of anesthetic can potentially reduce POCD. The authors performed this network meta-analysis to compare different anesthetic drugs in reducing the incidence of POCD for elderly people undergoing noncardiac surgery. We searched MEDLINE, EMBASE, the Cochrane Library, and the Web of Science for randomized controlled trials comparing the different anesthetic drugs for noncardiac surgery in elderly from inception until July, 2022. The protocol was registered on the PROSPERO database (CRD#42020183014). A total of 34 trials involving 4314 patients undergoing noncardiac surgery in elderly were included. The incidence of POCD for each anesthetic drug was placebo (27.7%), dexmedetomidine (12.9%), ketamine (15.2%), propofol (16.8%), fentanyl (23.9%), midazolam (11.3%), sufentanil (6.3%), sevoflurane (24.0%), and desflurane (28.3%). Pairwise and network meta-analysis showed dexmedetomidine was significantly reducing the incidence of POCD when compared with placebo. Network meta-analysis also suggested dexmedetomidine was significantly reducing the incidence of POCD when compared with sevoflurane. Sufentanil and dexmedetomidine ranked the first and second in reducing the incidence of POCD with the surface under the cumulative ranking curve value of 87.4 and 81.5%. Sufentanil and dexmedetomidine had the greatest possibility to reduce the incidence of POCD for elderly people undergoing noncardiac surgery.

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.

The impact of the coronavirus pandemic on sedation in critical care: volatile anesthetics in the ICU.

PURPOSE OF REVIEW: To reflect on the impact of the coronavirus pandemic on sedation for mechanically ventilated patients. RECENT FINDINGS: Shortages of intravenous sedatives during coronavirus pandemic renewed interest in using widely available inhaled anaesthetics for sedation of critically ill patients. Universally used for surgical anaesthesia, inhaled anaesthetics may offer therapeutic advantages in patients with acute lung injury with good sedation profiles, rapid clearance and lower lung inflammation in pilot trials. However, enabling ICU sedation with inhaled anaesthetics required technological and human resource innovation during the chaos of the global pandemic. The disruption of standard sedation practices is challenging during normal operations, yet pandemic facilitated innovation in this field by fostering cross-discipline collaboration supported by healthcare professionals, hospitals, research institutes and regulators. SUMMARY: Although further research is needed to establish the role of inhaled anaesthetics in critical care sedation toolkit, maintaining the spirit of innovation ignited during the recent coronavirus pandemic would require ongoing collaboration and streamlining of processes among healthcare, research and regulatory institutions.

Penthrox enables quicker management of fractures, dislocations and more: learning lessons from expedited care of trauma patients during the COVID-19 pandemic.

INTRODUCTION: Methoxyflurane is an historical anaesthetic agent that has undergone a renaissance with the introduction of a smaller dose in a handheld 'Penthrox' device. The benefits of Penthrox include its ease of use, with disposable individual packets, and the need for less monitoring and staff, when compared with deeper sedation. The literature acknowledges its use for analgesia and in the management of anterior shoulder dislocation but in no other procedural orthopaedic circumstance. METHODS: Following institutional approval, we undertook a retrospective review of all incidences of Penthrox use to facilitate minor procedures within a 2-month period starting 24 March 2020. Time to procedure and success were recorded using the surrogate markers of patient attendance and x-Ray occurrence times. RESULTS: Some 101 Penthrox doses were given to 89 patients over 97 unique episodes between 24 March and 26 May 2020. No complications were recorded following the use of Penthrox during this period. Patient demographics were explored. Fracture manipulations and casting (n=54) had a 100% success rate in achieving adequate and safe reduction. Joint dislocations (n=34) were treated with varying success. Native elbow dislocations were reduced most successfully (4/4, 100%). Native shoulder dislocations were seen in 17 patients and successful relocation was seen in 11 cases, giving a success rate of 65%. CONCLUSIONS: This is the first study, outside anterior shoulder dislocations, to report on the efficacy of Penthrox within emergent orthopaedic scenarios. We have demonstrated Penthrox to be a safe tool for helping to manage trauma procedures in the emergency department.

Evaluation of the effectiveness and costs of inhaled methoxyflurane versus usual analgesia for prehospital injury and trauma: non-randomised clinical study.

BACKGROUND: We aimed to investigate clinical benefits and economic costs of inhaled methoxyflurane when used by ambulance staff for prehospital emergency patients with trauma. Comparison is to usual analgesic practice (UAP) in the UK in which patient records were selected if treatment had been with Entonox® or intravenous morphine or intravenous paracetamol. METHODS: Over a 12-month evaluation period, verbal numerical pain scores (VNPS) were gathered from adults with moderate to severe trauma pain attended by ambulance staff trained in administering and supplied with methoxyflurane. Control VNPS were obtained from ambulance database records of UAP in similar patients for the same period. Statistical modelling enabled comparisons of methoxyflurane to UAP, where we employed an Ordered Probit panel regression model for pain, linked by observational rules to VNPS. RESULTS: Overall, 96 trained paramedics and technicians from the East Midlands Ambulance Service NHS Trust (EMAS) prepared 510 doses of methoxyflurane for administration to a total of 483 patients. Comparison data extracted from the EMAS database of UAP episodes involved: 753 patients using Entonox®, 802 patients using intravenous morphine, and 278 patients using intravenous paracetamol. Modelling results included demonstration of faster pain relief with inhaled methoxyflurane (all p-values < 0.001). Methoxyflurane's time to achieve maximum pain relief was estimated to be significantly shorter: 26.4 min (95%CI 25.0-27.8) versus Entonox® 44.4 min (95%CI 39.5-49.3); 26.5 min (95%CI 25.0-27.9) versus intravenous morphine 41.8 min (95%CI 38.9-44.7); 26.5 min (95%CI 25.1-28.0) versus intravenous paracetamol 40.8 (95%CI 34.7-46.9). Scenario analyses showed that durations spent in severe pain were significantly less for methoxyflurane. Costing scenarios showed the added benefits of methoxyflurane were achieved at higher cost, eg versus Entonox® the additional cost per treated patient was estimated to be £12.30. CONCLUSION: When administered to adults with moderate or severe pain due to trauma inhaled methoxyflurane reduced pain more rapidly and to a greater extent than Entonox® and parenteral analgesics. Inclusion of inhaled methoxyflurane to the suite of prehospital analgesics provides a clinically useful addition, but one that is costlier per treated patient.

Volatile versus Propofol General Anesthesia and Long-term Survival after Breast Cancer Surgery: A National Registry Retrospective Cohort Study.

BACKGROUND: Several retrospective studies using administrative or single-center data have failed to show any difference between general anesthesia using propofol versus inhaled volatiles on long-term survival after breast cancer surgery. Although randomized controlled trials are ongoing, validated data from national clinical registries may advance the reliability of existing knowledge. METHODS: Data on breast cancer surgery performed under general anesthesia between 2013 and 2019 from the Swedish PeriOperative Registry and the National Quality Registry for Breast Cancer were record-linked. Overall survival was compared between patients receiving propofol and patients receiving inhaled volatile for anesthesia maintenance. RESULTS: Of 18,674 subjects, 13,873 patients (74.3%) received propofol and 4,801 (25.7%) received an inhaled volatile for general anesthesia maintenance. The two cohorts differed in most respects. Patients receiving inhaled volatile were older (67 yr vs. 65 yr), sicker (888 [19.0%] American Society of Anesthesiologists status 3 to 5 vs. 1,742 [12.8%]), and the breast cancer to be more advanced. Median follow-up was 33 months (interquartile range, 19 to 48). In the full, unmatched cohort, there was a statistically significantly higher overall survival among patients receiving propofol (13,489 of 13,873 [97.2%]) versus inhaled volatile (4,039 of 4,801 [84.1%]; hazard ratio, 0.80; 95% CI, 0.70 to 0.90; P < 0.001). After 1:1 propensity score matching (4,658 matched pairs), there was no statistically significant difference in overall survival (propofol 4,284 of 4,658 [92.0%]) versus inhaled volatile (4,288 of 4,658 [92.1%]; hazard ratio, 0.98; 95% CI, 0.85 to 1.13; P = 0.756). CONCLUSIONS: Among patients undergoing breast cancer surgery under general anesthesia, no association was observed between the choice of propofol or an inhaled volatile maintenance and overall survival.

GLP-1 Analog Alleviated Cognitive Dysfunction in Aged Rats Anaesthetized with Sevoflurane.

Postoperative cognitive dysfunction (POCD) in elderly patients undergoing general anesthesia is a major problem in the aging society. Sevoflurane is the most widely applied anesthetic in clinical practice. In this study, we investigated the effects of the GLP-1 analogue liraglutide on cognitive function in aged rats anesthetized by sevoflurane. Specifically, 48 Sprague-Dawley rats were divided into the control (C) group, the liraglutide (L) group, the sevoflurane (S) group, and the sevoflurane+liraglutide (SL) group, each group with 12 rats. In the S group and the SL group, the rats were injected subcutaneously with normal saline and liraglutide after inhalation of a mixture of 3% sevoflurane and pure oxygen. In the C group and the L group, normal saline and liraglutide were injected subcutaneously into the rats after inhalation of pure oxygen. Morris Water Maze Task was applied for the detection of spatial learning and memory in rats; HE and TUNEL for staining; and western blot for quantifying Bax, Bcl-2 expression, and examining caspase-3 activity in hippocampal tissues as well as for revealing the antiapoptotic mechanism. Besides, the accumulation of inflammatory factors NF-κB and IL-1ß in the hippocampal tissue was quantitatively studied to reveal the anti-inflammatory mechanism. The protective effect of liraglutide on sevoflurane toxicity was the first to be confirmed in this study. Additionally, this study elucidated the mechanism of the above effect. The results of this study might be helpful to find an effective medical solution for the treatment of POCD caused by sevoflurane anesthesia.