Superior gallstone dissolubility and safety of tert-amyl ethyl ether over methyl-tertiary butyl ether.

BACKGROUND: The use of methyl-tertiary butyl ether (MTBE) to dissolve gallstones has been limited due to concerns over its toxicity and the widespread recognition of the safety of laparoscopic cholecystectomy. The adverse effects of MTBE are largely attributed to its low boiling point, resulting in a tendency to evaporate. Therefore, if there is a material with a higher boiling point and similar or higher dissolubility than MTBE, it is expected to be an attractive alternative to MTBE. AIM: To determine whether tert-amyl ethyl ether (TAEE), an MTBE analogue with a relatively higher boiling point (102 °C), could be used as an alternative to MTBE in terms of gallstone dissolubility and toxicity. METHODS: The in vitro dissolubility of MTBE and TAEE was determined by measuring the dry weights of human gallstones at predetermined time intervals after placing them in glass containers with either of the two solvents. The in vivo dissolubility was determined by comparing the weights of solvent-treated gallstones and control (dimethyl sulfoxide)-treated gallstones, after the direct infusion of each solvent into the gallbladder in both hamster models with cholesterol and pigmented gallstones. RESULTS: The in vitro results demonstrated a 24 h TAEE-dissolubility of 76.7%, 56.5% and 38.75% for cholesterol, mixed, and pigmented gallstones, respectively, which represented a 1.2-, 1.4-, and 1.3-fold increase in dissolubility compared to that of MTBE. In the in vitro experiment, the 24 h-dissolubility of TAEE was 71.7% and 63.0% for cholesterol and pigmented gallstones, respectively, which represented a 1.4- and 1.9-fold increase in dissolubility compared to that of MTBE. In addition, the results of the cell viability assay and western blot analysis indicated that TAEE had a lower toxicity towards gallbladder epithelial cells than MTBE. CONCLUSION: We demonstrated that TAEE has higher gallstone dissolubility properties and safety than those of MTBE. As such, TAEE could present an attractive alternative to MTBE if our findings regarding its efficacy and safety can be consistently reproduced in further subclinical and clinical studies.

Reduction of oxidative stress a key for enhanced postoperative recovery with fewer complications in esophageal surgery patients: Randomized control trial to investigate therapeutic impact of anesthesia management and usefulness of simple blood test for prediction of high-risk patients.

BACKGROUND: Oxidative stress may be an integral determinant of surgical stress severity. We examined whether the preoperative level of derivatives of reactive oxygen metabolites (d-ROMs), an oxidative stress biomarker based on total hydroperoxides in circulating blood, is predictive of increased risk of delayed recovery and complications after surgery, as well as the effects of anesthesia management on postoperative recovery in light of oxidative stress. METHODS: Patients (American Society of Anesthesiologists physical status I-II) scheduled for a radical esophagectomy (n = 186) were randomly selected to receive inhalational sevoflurane (n = 94) or intravenous propofol (n = 92) anesthesia. Preoperative blood d-ROMs level, as well as pre-and postoperative plasma ferric-reducing ability, were analyzed to assess oxidative stress, with white blood cell (WBC) count, C-reactive protein (CRP) level, incidence of severe postoperative complications, and postoperative recovery process within 30 days after surgery also examined in a double-blind fashion. RESULTS: Postoperative normalization of WBC and CRP was extended in patients with elevated preoperative d-ROMs [WBC versus d-ROMs: correlation coefficient (r) = 0.58 P < .001; CRP versus d-ROMs: r = 0.46 P < .001]. Receiver operating characteristics analysis of d-ROMs in relation to incidence of severe postoperative complications revealed an optimum d-ROMs threshold value of 410 UCarr and that patients with ≥410 UCarr had a greater risk of complications as compared to those with lower values (odds ratio = 4.7). Plasma ferric-reducing ability was decreased by 61 ±â€Š185 mmol·l (P < .001) after surgery, demonstrating development of surgery-related oxidative stress, the magnitude of which was positively correlated with preoperative d-ROMs level (r = 0.16, P = .043). A comparison of the 2 anesthesia management protocols showed that patients who received propofol, an antioxidant anesthetic, had no postoperative decrease in ferric-reducing ability, lower incidence of severe postoperative complications (7 of 92 versus 18 of 94, P = .030, odds ratio = 0.35), and faster uneventful recovery time (WBC normalization days 7.1 ±â€Š5.2 versus 13.6 ±â€Š10.2, P < .001) as compared to those who received sevoflurane. CONCLUSIONS: Elevated preoperative blood d-ROMs predicts greater intraoperative oxidative stress and increased postoperative complications with prolonged recovery, thus is useful for identifying high-risk patients for delayed and complicated surgical recovery. Reduction of oxidative stress is vital for enhanced recovery, with control by antioxidants such as propofol a possible solution.

Equipment failure of intravenous syringe pump detected by increase in Narcotrend stage: A case report.

RATIONALE: Awareness is the recovery of consciousness during general anesthesia. It occurs when patients under general anesthesia receive inadequate anesthetic medications to maintain unconsciousness during surgery. Equipment failure is a common cause of intraoperative awareness. PATIENT CONCERNS: A 16-year-old boy, 85 kg in weight, was admitted to our hospital for thyroglossal cystectomy under general anesthesia. Six minutes after the intubation, we noted that the Narcotrend index indicated a condition of light anesthesia and the patient was observed to be in tears. DIAGNOSIS: Improper positioning of the syringe fixing clamp on the CP700TCI infusion pump caused equipment failure and light anesthesia. INTERVENTIONS: Bolus of 50 mg propofol and 2 mg midazolam were administered manually by syringe, and inhalation of 2% sevoflurane was supplemented. Infusion pump was replaced. OUTCOMES: The Narcotrend index of the patient returned to state of deep anesthesia following manual administration of the anesthetic medications. Following the surgery, the patient had an uneventful recovery, and did not present with evidence of awareness. LESSONS: Users of the CP700TCI syringe pump should pay attention to the position of the syringe fixing clamp. Anesthesiologists should check all the equipment according to a defined checklist prior to anesthesia. Narcotrend monitor could help to detect light anesthesia and prevent potential awareness.

Comparison of three different ketofol proportions in children undergoing dental treatment.

AIM AND BACKGROUND: Sedation is gaining popularity among dental procedures in children. Ketamine and propofol mixture, known as ketofol, is one of the promising choices in sedation protocols; however, there is no consensus on the exact ratio of ketamine plus propofol especially in dental practice. The aim of present study was to compare perioperative side effect profiles, recovery profiles, and satisfaction rates of both parents' and dentists' following three different ratio of ketofol mixtures in children undergoing dental treatment. Materials and. METHODS: Three study groups each containing 30 children scheduled for dental treatment were created. Following anesthesia induction with 5% sevoflurane, 50% nitrous oxide mixture in 50% oxygen, 1 mg/kg bolus ketofol dose was administered. Patients in Group 1 received ketofol as a 1:1 mixture, patients in Group 2 received 1:2 ketofol while in Group 3; 1:4 ketofol was administered at a constant dose of 100 µg/kg/min. Additional doses of the ketofol solution at the same concentration with infused solutions in groups (0.5 mg/kg from either 1:1, 1:2, or 1:4 proportions) were administered if required. Perioperative vital signs, side effects, postoperative side effects, recovery durations, parents' and dentists' satisfaction levels were compared between groups. RESULTS: There were no significant differences between groups in terms of perioperative vital signs and side effects. Depth of sedation, dentists' satisfaction levels and postoperative side effects -myoclonus, hypersalivation and tachycardia were significantly higher in Group 1. Parents' satisfaction was highest in Group 3, however, necessity of additional doses and dissatisfaction of dentists' were found highest in this group. Mean duration of recovery recorded in Group 3 was shortest compared with other groups. CONCLUSION: Decreased ketamine doses in ketofol mixture was related with decreased side effect profile, high parents' satisfaction with fast recovery, however, dentists' satisfaction was lower. In this context, results of present study indicated that ketofol mixture of 1:2 ratio was more reliable choice than others when all investigated parameters evaluated simultaneously.

Sevoflurane is an effective adjuvant to propofol-based total intravenous anesthesia for attenuating cough reflex in nonintubated video-assisted thoracoscopic surgery.

BACKGROUND: Nonintubated video-assisted thoracic surgery (VATS) has been widely developed during the recent years. Cough reflex is an inevitably encountered problem while approaching lung lesions, and it may induce major bleeding. Sevoflurane anesthesia may attenuate cough reflex by inhibiting the pulmonary irritant receptors. However, the incidence of postoperative nausea and vomiting (PONV) in inhalational anesthesia is higher than in the propofol-based total intravenous anesthesia (TIVA). We investigated the effect of sevoflurane combination with propofol-based TIVA on cough reflex and PONV in nonintubated VATS. METHODS: Ninety patients undergoing nonintubated VATS with laryngeal mask airway (LMA) and spontaneous breathing were randomly assigned for TIVA or propofol/sevoflurane anesthesia. In the TIVA group (n = 45), anesthesia was induced and maintained with propofol and fentanyl; in the propofol/sevoflurane (P/S) group (n = 45), 1% sevoflurane anesthesia was added to propofol and fentanyl anesthesia. The primary outcome measurements were cough reflex. In addition, the incidence of PONV and extubation time were investigated. RESULTS: Patients with cough reflex were significantly fewer in the P/S group than in the TIVA group (10/45 vs 34/45; P < .001). The cough severity (35/5/5/0 vs 11/17/17/0; P < .001) and limb movement (40/5/0/0 vs 28/17/0/0; P < .001) were lower in the P/S group than in the TIVA group. Besides, incremental fentanyl bolus for cough reflex was 5 (0 [0-1]) in the P/S group and 17 (0 [0-3]) in the TIVA group (P < .05). And there was no conversion to general anesthesia, postoperative hemorrhage, aspiration pneumonia, or PONV in the 2 groups. Besides, there was no significant difference in extubation time (TIVA: 5.04 ±â€Š2.88 vs P/S: 4.44 ±â€Š2.98 minutes; P = .33). CONCLUSION: Sevoflurane attenuated cough reflex under propofol-based TIVA and did not increase the incidence of PONV and extubation time in nonintubated VATS.

Cardiac troponin I in dogs anaesthetized with propofol and sevoflurane: the influence of medetomidine premedication and inspired oxygen fraction.

OBJECTIVE: To investigate changes in serum cardiac troponin I (cTnI) concentrations in dogs in which medetomidine was used for sedation or for premedication prior to anaesthesia with propofol and sevoflurane. STUDY DESIGN: Prospective clinical study. ANIMALS: A total of 66 client-owned dogs. METHODS: The dogs were sedated with medetomidine (0.04 mg kg-1) intravenously (IV) (group M; n = 20) and left to breath room air or anaesthetized with propofol (6.5 ± 0.76 mg kg-1 IV) and sevoflurane (4.5% vaporizer setting) in oxygen (group P + S; n = 20) or with medetomidine (0.04 mg kg-1 IV), propofol (1.92 ± 0.63 mg kg-1) and sevoflurane (3% vaporizer setting) in oxygen (group M + P + S; n = 26), respectively. After 35 minutes, medetomidine was antagonized with atipamezole (0.1 mg kg-1 intramuscularly). Blood samples for serum cTnI determination were taken before sedation or anaesthesia, 6 and 12 hours and 4 days thereafter. Serum cTnI concentrations were measured with the Architect STAT Troponin-I assay. RESULTS: Before sedation or anaesthesia, cTnI concentrations were above the detection limit in 22 out of 66 (33%) of dogs. Compared to basal values, cTnI concentrations significantly increased at 6 and 12 hours in all groups and at day 4 in group M. There were no differences in cTnI concentration between groups at baseline, at 6 hours and at 4 days. At 12 hours, cTnI concentrations were significantly higher in groups M and P + S, respectively, compared to group M + P + S. CONCLUSIONS AND CLINICAL RELEVANCE: Oxygenation during anaesthesia and reduction of propofol and sevoflurane dose due to the sparing effects of medetomidine might have played a role in alleviation of myocardial hypoxic injury as indicated by the less severe and short-lived increase of cTnI in the M + P + S group.

The analgesic effects of intraoperative total intravenous anesthesia (TIVA) with propofol versus sevoflurane after colorectal surgery.

Clinical studies have shown that total intravenous anesthesia (TIVA) with propofol is associated with better postoperative pain control compared with inhalational anesthesia, while other studies have not shown any benefit. The analgesic effect of TIVA with propofol in colorectal surgery has not been studied. The aim of this study is to evaluate the postoperative analgesic effects of TIVA with propofol versus inhalational sevoflurane in colorectal surgery.This is a retrospective case-control study. Records of patients undergoing colorectal surgery from 2014 to 2016 (36 months) were retrieved. Ninety-five patients who received TIVA with propofol were matched against 95 patients who received inhalational sevoflurane. Acute postoperative numerical rating scale (NRS) pain scores, postoperative morphine consumption, patient satisfaction, and side effects were compared and analyzed for differences between TIVA with propofol and sevoflurane.There were no significant differences in NRS pain scores, incidence of side effects, and patient satisfaction between the 2 groups. Patients receiving TIVA with propofol had significantly reduced total morphine consumption (P < .001), and daily morphine consumption on postoperative days 1 (P = .031), 2 (P = .002), and 3 (P = .031) compared with those receiving sevoflurane.TIVA with propofol was not associated with improved postoperative analgesia, better patient satisfaction, or reduced side effects. It may reduce postoperative opioid consumption after colorectal surgery.

Acute presentation of a partially obstructing laryngeal tumour: adjuvant agents to gaseous induction of anaesthesia.

We present the case of a 53-year-old man who attended our emergency department with stridor. He had recently undergone investigation for possible glottic cancer. We discuss the airway management of such a case. We believe this to be the first description of propofol target controlled infusion and clonidine to supplement a sevoflurane gas induction, in order to obtund response to intubation while maintaining spontaneous ventilation. We also consider how airway interventions may impact prognosis and need to be considered.

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

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

Determination of the minimum alveolar concentration (MAC) and cardiopulmonary effects of sevoflurane in sheep.

OBJECTIVE: To determine sevoflurane's minimum alveolar concentration (MACSEVO) and its cardiopulmonary effects in sheep. STUDY DESIGN: Prospective experimental study. ANIMALS: A group of 10 female nonpregnant Sardinian milk sheep. METHODS: Anesthesia was induced in each sheep twice with sevoflurane in oxygen. After a 30 minute equilibration at end-tidal sevoflurane concentration (Fe'Sevo) of 2.8%, an electrical stimulus (5 Hz/1 ms/50 mA) was applied to the right thoracic limb for 1 minute or until gross purposeful movement occurred. The Fe'Sevo was then changed using a 0.2% up-and-down protocol, dependent on whether or not the response was positive, and then noxious stimulation was repeated. The MACSEVO was defined as the mean Fe'Sevo between that allowing purposeful movement and that not. The group of 10 sheep were re-anesthetized and MACSEVO was re-determined. Thereafter, Fe'Sevo was maintained for 15 minutes each at concentrations corresponding to 1.0, 1.3, 1.6, 1.9 and 0.75 MACSEVO multiples, and cardiopulmonary, blood gas, acid-base variables and plasma electrolytes were determined. Also, time to induction of anesthesia, extubation and recovery were recorded. RESULTS: The mean ± standard deviation of the MACSEVO was 2.74 ± 0.38%. Median (interquartile range) time to intubation was 3.13 (2.98-3.33) minutes, time to extubation was 6.85 ± 2.65 minutes and time to recovery was 13.4 ± 5.2 minutes. With increasing Fe'Sevo, arterial blood pressures progressively decreased as did minute ventilation, which in turn caused end-tidal carbon dioxide, arterial partial pressure of carbon dioxide and bicarbonate values to steadily increase without significantly affecting arterial partial pressure of oxygen. CONCLUSIONS AND CLINICAL RELEVANCE: The reported MACSEVO agrees with published data in this and other species. Administration of sevoflurane in sheep caused marked hemodynamic and respiratory depression, but soon after turning off the vaporizer, sheep could be extubated and recovered rapidly and event-free.

Visual evoked potentials can be reliably recorded using noninvasive epidermal electrodes in the anesthetized rat.

PURPOSE: Visual evoked potentials (VEPs) are a powerful tool to evaluate nervous conduction along the visual pathways, both in humans and in animal models. Traditionally, epidural screw electrodes are used to record VEPs in preclinical research. Here we tested the feasibility in the preclinical setting of the same noninvasive technique used for clinical VEP acquisition, by using epidermal cup electrodes with no surgical procedures. METHODS: Monocular flash VEPs were recorded bilaterally under sevoflurane anesthesia once a week for 6 weeks in 14 dark Agouti rats, 7 with implanted epidural screws and 7 with epidermal 6 mm Ø Ag/AgCl cups. RESULTS: VEP traces obtained with the two techniques were morphologically comparable. There were no significant differences in latency of the main visual component between screw-recorded VEPs (sVEPs) and cup-recorded VEPs (cVEPs). Amplitude values with epidermal cups were significantly lower than those with epidural screws. Both techniques provided latencies and amplitudes which were stable over time. Furthermore, with regard to latency both methods ensured highly repeatable measurements over time, with epidermal cups even providing slightly better results. On the other hand, considering amplitudes, cVEPs and sVEPs provided fairly acceptable repeatability. CONCLUSIONS: Epidermal cup electrodes can provide comparable results to those obtained with the "gold standard" epidural screws, while representing a simpler and less invasive technique to test nervous conduction along the visual pathways in the preclinical setting.

Recovery of Endothelial Function after Minor-to-Moderate Surgery Is Impaired by Diabetes Mellitus, Obesity, Hyperuricemia and Sevoflurane-Based Anesthesia.

Endothelial dysfunction is observed in several cardiovascular diseases, where endothelium-dependent vasodilation is impaired by oxidative stress. However, the time course of endothelial function during the perioperative period of a minor-to-moderate surgery, and the effects of atherosclerotic risk factors and employed general anesthetics on recovery of endothelial function, are unknown. Endothelial function of 30 patients was evaluated as the reactive hyperemia index (RHI) of reactive hyperemia peripheral arterial tonometry. RHI was measured on day before surgery (control), immediately after surgery (Day 0), day after surgery (Day 1), and day 4 after surgery (Day 4) in patients with no functional limitations who were scheduled for oral and maxillofacial surgery of around 3 hours. Sevoflurane- or propofol-based anesthesia supplemented with an opioid analgesic remifentanil was employed. The control RHI was 2.26 ± 0.64. The RHI significantly decreased to the lowest level on Day 0 (1.52 ± 0.28), recovered on Day 1 (2.07 ± 0.58), and improved further on Day 4 (2.55 ± 0.83). Multiple linear regression analysis revealed that recovery of the RHI from Day 0 to Day 4 was impaired by diabetes mellitus (P = 0.0313), obesity (BMI ≥ 25; P = 0.0166), hyperuricemia (uric acid ≥ 6.0 mg/dL; P = 0.0416) and sevoflurane-based anesthesia (P = 0.0308). These findings suggest that endothelial function as evaluated by the RHI is severely suppressed on the day of a minor-to-moderate surgery, and that it improves until the 4th postoperative day on average. Recovery of endothelial function is impaired by diabetes mellitus, obesity, hyperuricemia, and sevoflurane-based anesthesia.

Upregulation of vascular endothelial growth factor receptor-1 contributes to sevoflurane preconditioning-mediated cardioprotection.

PURPOSE: Sevoflurane preconditioning (SPC) can provide myocardial protective effects similar to ischemic preconditioning. However, the exact mechanism of SPC remains unclear. Previous studies indicate that vascular endothelial growth factor receptor 1 (VEGFR-1) is involved in ischemic preconditioning-mediated cardioprotection. This study was designed to determine the significance of VEGFR-1 signaling in SPC-mediated cardioprotection. MATERIALS AND METHODS: Myocardial ischemia-reperfusion (I/R) rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, after 15 min of baseline equilibration, the isolated hearts were pretreated with 2.5% sevoflurane, 2.5% sevoflurane+MF1 10 µmol/L, or 2.5% sevoflurane+placental growth factor 10 µmol/L, and then subjected to 30 min of global ischemia and 120 min of reperfusion. The changes in hemodynamic parameters, myocardial infarct size, and the levels of creatine kinase-MB, lactate dehydrogenase, cardiac troponin-I, tumor necrosis factor-α, and interleukin 6 in the myocardium were evaluated. RESULTS: Compared to the I/R group, pretreatment with 2.5% sevoflurane significantly improved the cardiac function, limited myocardial infarct size, reduced cardiac enzyme release, upregulated VEGFR-1 expression, and decreased inflammation. In addition, the selective VEGFR-1 agonist, placental growth factor, did not enhance the cardioprotection and anti-inflammation effects of sevoflurane, while the specific VEGFR-1 inhibitor, MF1, completely reversed these effects. CONCLUSION: Our data have demonstrated that 2.5% sevoflurane preconditioning alleviates heart I/R injury, which is probably mediated by the anti-inflammatory property and upregulation of VEGFR-1.

Effectiveness and Safety of a Novel Approach for Management of Patients with Potential Difficult Mask Ventilation and Tracheal Intubation: A Multi-center Randomized Trial.

BACKGROUND:: Patients with potential difficult mask ventilation (DV) and difficult intubation (DI) are often managed with awake intubation, which can be stressful for patients and anesthesiologists. This prospective randomized study evaluated a new approach, fast difficult airway evaluation (FDAE). We hypothesized that the FDAE approach would reduce the need for awake intubation. METHODS:: After obtaining informed consent, 302 patients with potential DV/DI undergoing elective surgeries were randomly assigned to the FDAE group (Group E) and the control group (Group C). In Group E, patients were gradually sedated, and adequacy of manual mask ventilation during spontaneous breathing was assessed at various sedation levels. Awake intubation was applied in those with inadequate mask ventilation. In Group C, DI was evaluated under local anesthesia. However, the care team could intubate under general anesthesia if the vocal cords were visible. The primary outcome was the rate of awake intubations in both groups and the induction efficiency assessed by the induction time. The secondary outcome was the incidence of serious complications. RESULTS: The rate of awake intubation was significantly lower in Group E than that in Group C (5.81% vs. 36.05%, χ2 = 42.3, P < 0.001). The induction time was much shorter in Group E than in Group C (11.85 ± 4.82 min vs. 18.71 ± 7.85 min, t = 5.39, P < 0.001). There was no significant difference in the incidence of intubation related complications between the two groups. Patients in Group E had a much lower incidence of recall (9.68% vs. 44.90%, χ2 = 47.68, P < 0.001) of the induction process and higher satisfaction levels than patients in Group C (t = 15.36, P < 0.001). CONCLUSIONS: The FDAE significantly reduces the need for awake intubation and improves the efficiency of the intubation process without comprising safety in patients with potential difficult mask ventilation and DI. TRIAL REGISTRATION:: No. ChiCTR-TRC-11001418; http://www.gctr.org/cn/proj/show.aspx?proj=1562.

MiR-34a-5p mediates sevoflurane preconditioning induced inhibition of hypoxia/reoxygenation injury through STX1A in cardiomyocytes.

Anesthetic preconditioning is a cellular protective approach whereby exposure to a volatile anesthetic renders cardio injury. Sevoflurane preconditioning has been shown to exhibit cardio protective effect on hypoxia/reoxygenation (H/R) injury, but the underlying mechanism is unclear. Syntaxin 1A (STX1A), an important regulator in cardio disease, was predicted to be the target gene of microRNA-34a-5p (miR-34a-5p). The current research was designed to delineate the role of miR-34a-5p in regulating sevoflurane preconditioning in cardiomyocytes injury. In this study, the results demonstrated that the expression of STX1A was significantly increased, while miR-34a-5p was dramatically decreased in sev-preconditioning H9c2 cells as compared with cells only under H/R stimulation. Moreover, miR-34a-5p regulated the protective effect of sev-preconditioning in injured H9c2 cells by mediating cell proliferation and cell apoptosis. Additionally, the luciferase report confirmed the targeting reaction between STX1A and miR-34a-5p. Taken together, our study suggested that miR-34a-5p regulated sev-preconditioning induced inhibition of hypoxia/reoxygenation injury through mediating STX1A, provided a potential therapeutic target for anesthetic protection in cardio disease.

Sevoflurane posttreatment prevents oxidative and inflammatory injury in ventilator-induced lung injury.

Mechanical ventilation is a life-saving clinical treatment but it can induce or aggravate lung injury. New therapeutic strategies, aimed at reducing the negative effects of mechanical ventilation such as excessive production of reactive oxygen species, release of pro-inflammatory cytokines, and transmigration as well as activation of neutrophil cells, are needed to improve the clinical outcome of ventilated patients. Though the inhaled anesthetic sevoflurane is known to exert organ-protective effects, little is known about the potential of sevoflurane therapy in ventilator-induced lung injury. This study focused on the effects of delayed sevoflurane application in mechanically ventilated C57BL/6N mice. Lung function, lung injury, oxidative stress, and inflammatory parameters were analyzed and compared between non-ventilated and ventilated groups with or without sevoflurane anesthesia. Mechanical ventilation led to a substantial induction of lung injury, reactive oxygen species production, pro-inflammatory cytokine release, and neutrophil influx. In contrast, sevoflurane posttreatment time dependently reduced histological signs of lung injury. Most interestingly, increased production of reactive oxygen species was clearly inhibited in all sevoflurane posttreatment groups. Likewise, the release of the pro-inflammatory cytokines interleukin-1ß and MIP-1ß and neutrophil transmigration were completely prevented by sevoflurane independent of the onset of sevoflurane administration. In conclusion, sevoflurane posttreatment time dependently limits lung injury, and oxidative and pro-inflammatory responses are clearly prevented by sevoflurane irrespective of the onset of posttreatment. These findings underline the therapeutic potential of sevoflurane treatment in ventilator-induced lung injury.

The effect of propofol and sevoflurane on cancer cell, natural killer cell, and cytotoxic T lymphocyte function in patients undergoing breast cancer surgery: an in vitro analysis.

BACKGROUND: To clarify the effect of anaesthetic agents on cancer immunity, we evaluated the effects of propofol and sevoflurane on natural killer (NK) cell, cytotoxic T lymphocyte (CTL) counts and apoptosis rate in breast cancer and immune cells co-cultures from patients who underwent breast cancer surgery. METHODS: Venous blood samples were collected after inducing anaesthesia and at 1 and 24 h postoperatively in patients who had undergone breast cancer surgery. The patients were allocated randomly to the propofol- or sevoflurane-based anaesthesia groups. We counted and detected apoptosis in cancer cell, NK cell and CTL of patients with breast cancer by co-culture with a breast cancer cell line in both groups. We also evaluated changes in the cytokines tumour necrosis factor-alpha, interleukin (IL)-6 and IL-10 during the perioperative period. RESULTS: Forty-four patients were included in the final analysis. No difference in NK cell count, CTL count or apoptosis rate was detected between the groups. Furthermore, the number of breast cancer cells undergoing apoptosis in the breast cancer cell co-cultures was not different between the groups. No changes in cytokines were detected between the groups. CONCLUSION: Although basic science studies have suggested the potential benefits of propofol over a volatile agent during cancer surgery, propofol was not superior to sevoflurane, on the aspects of NK and CTL cells counts with apoptosis rate including breast cancer cell, during anaesthesia for breast cancer surgery in a clinical environment. TRIAL REGISTRATION: NCT02758249 on February 26, 2016.

Pain and analgesic drugs in chronic venous ulcers with topical sevoflurane use.

OBJECTIVE: Pain in chronic venous ulcers (CVUs) notably increases with the usual cleaning of the wound. Chronic pain is usually poorly controlled even with the multiple analgesic treatments available. Analgesics can have different serious adverse effects and medical interactions in old patients with several comorbidities. This study reports the efficacy and safety of topical sevoflurane for treatment of pain in CVUs. METHODS: We report a descriptive and retrospective study of 30 patients older than 65 years with painful CVUs refractory to conventional analgesic treatments. Patients received topical sevoflurane treatment before the usual cleaning of the ulcer. Cleaning visits with sevoflurane every 2 days for a period of 1 month were scheduled. We compared the visual analog scale results and analgesic drugs for cleaning with and without topical sevoflurane. The systemic pharmacokinetics of sevoflurane after topical application has not been determined. RESULTS: Pain related to CVUs decreased with topical sevoflurane. Sevoflurane had an analgesic effect with latency time between 2 and 7 minutes. The duration of analgesia ranged between 8 and 18 hours. The time needed to take an analgesic treatment increased after application of sevoflurane. The use of other conventional analgesic drugs, including paracetamol, metamizole, nonsteroidal anti-inflammatory drugs, tramadol, and major opioids, was progressively reduced. The main local adverse effects were mild and transient, including heat, pruritus, and erythema. There were no systemic adverse effects. CONCLUSIONS: Topical sevoflurane has an intense, fast, and long-lasting local analgesic effect with an adequate safety profile. It also diminishes the taking of other conventional analgesic drugs. Topical sevoflurane is an efficient and safe therapeutic alternative for refractory painful CVUs.

Mid-gestational sevoflurane exposure inhibits fetal neural stem cell proliferation and impairs postnatal learning and memory function in a dose-dependent manner.

Advancements in fetal intervention procedures have led to increases in the number of pregnant women undergoing general anesthesia during the second trimester-a period characterized by extensive proliferation of fetal neural stem cells (NSCs). However, few studies have investigated the effects of mid-gestational sevoflurane exposure on fetal NSC proliferation or postnatal learning and memory function. In the present study, pregnant rats were randomly assigned to a control group (C group), a low sevoflurane concentration group (2%; L group), a high sevoflurane concentration group (3.5%; H group), a high sevoflurane concentration plus lithium chloride group (H + Li group), and a lithium chloride group (Li group) at gestational day 14. Rats received different concentrations of sevoflurane anesthesia for 2 h. The offspring rats were weaned at 28 days for behavioral testing (i.e., Morris Water Maze [MWM]), and fetal brains or postnatal hippocampal tissues were harvested for immunofluorescence staining, real-time PCR, and Western blotting analyses in order to determine the effect of sevoflurane exposure on NSC proliferation and the Wnt/ß-catenin signaling pathway. Our results indicated that maternal exposure to 3.5% sevoflurane (H group) during the mid-gestational period impaired the performance of offspring rats in the MWM test, reduced NSC proliferation, and increased protein levels of fetal glycogen synthase kinase-3 beta (GSK-3ß). Such treatment also decreased levels of ß-catenin protein, CD44 RNA, and Cyclin D1 RNA relative to those observed in the C group. However, these effects were transiently attenuated by treatment with lithium chloride. Conversely, maternal exposure to 2% sevoflurane (L group) did not influence NSC proliferation or the Wnt signaling pathway. Our results suggest that sevoflurane exposure during the second trimester inhibits fetal NSC proliferation via the Wnt/ß-catenin pathway and impairs postnatal learning and memory function in a dose-dependent manner.

Intravenous dexmedetomidine pre-medication reduces the required minimum alveolar concentration of sevoflurane for smooth tracheal extubation in anesthetized children: a randomized clinical trial.

BACKGROUND: It has been known that Dexmedetomidine pre-medication enhances the effects of volatile anesthetics, reduces the need of sevoflurane, and facilitates smooth extubation in anesthetized children. This present study was designed to determine the effects of different doses of intravenous dexmedetomidine pre-medication on minimum alveolar concentration of sevoflurane for smooth tracheal extubation (MACEX) in anesthetized children. METHODS: A total of seventy-five pediatric patients, aged 3-7 years, ASA physical status I and II, and undergoing tonsillectomy were randomized to receive intravenous saline (Group D0), dexmedetomidine 1 µg∙kg-1 (Group D1), or dexmedetomidine 2 µg∙kg-1 (Group D2) approximately 10 min before anesthesia start. Sevoflurane was used for anesthesia induction and anesthesia maintenance. At the end of surgery, the initial concentration of sevoflurane for smooth tracheal extubation was determined according to the modified Dixon's "up-and-down" method. The starting sevoflurane for the first patient was 1.5% in Group D0, 1.0% in Group D1, and 0.8% in Group D2, with subsequent 0.1% up or down in next patient based on whether smooth extubation had been achieved or not in current patient. The endotreacheal tube was removed after the predetermined concentration had been maintained constant for ten minutes. All responses ("smooth" or "not smooth") to tracheal extubation and respiratory complications were assessed. RESULTS: MACEX values of sevoflurane in Group D2 (0.51 ± 0.13%) was significantly lower than in Group D1 (0.83 ± 0.10%; P < 0.001), the latter being significantly lower than in Group D0 (1.40 ± 0.12%; P < 0.001). EC95 values of sevoflurane were 0.83%, 1.07%, and 1.73% in Group D2, Group D1, and Group D0, respectively. No patient in the current study had laryngospasm. CONCLUSION: Dexmedetomidine decreased the required MACEX values of sevoflurane to achieve smooth extubation in a dose-dependent manner. Intravenous dexmedetomidine 1 µg∙kg-1 and 2 µg∙kg-1 pre-medication decreased MACEX by 41% and 64%, respectively. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR-IOD-17011601 , date of registration: 09 Jun 2017, retrospectively registered.