Sevoflurane Administration Research Articles

Factors associated with the presence of postoperative headache in elective surgery patients: a prospective single center cohort study.

Headache is an important cause of minor postoperative morbidity. In this study we evaluated the association of anesthesia and surgery with the occurrence of postoperative headache in elective surgery patients. After obtaining ethical approval, 446 patients were enrolled in this prospective, single-centre cohort study. Participants were interviewed preoperatively, and for five days postoperatively, regarding the appearance of headache, while demographics, lifestyle, type of anesthesia and surgery, the anesthetic drugs administered and intraoperative adverse effects were recorded. Multiple logistic regression analysis was conducted in order to identify independent factors associated with postoperative headache, both in the total sample and in patients without previous history of headache. The observed overall frequency of postoperative headache was 28.3% (N=126) in the total sample. In patients with previous history of headache, the frequency of postoperative headache was 41% (N=89), while in those with no history the frequency of postoperative headache was 16.2% (N=37). Female gender [p=0.024; odds ratio (OR)=2.1], sevoflurane administration (p<0.001; OR=3.66), intraoperative hypotension (p=0.008; OR=2.12) and smoking (p=0.006; OR=1.74) were independently associated with postoperative headache. In patients without previous history, female gender (p=0.005; OR=4.77), sevoflurane administration (p=0.001; OR=6.9), intraoperative hypotension (p=0.006; OR=6.7) and caffeine consumption (p=0.041; OR=5.28) presented greater likelihood for postoperative headache, while smoking revealed no association. Female gender, sevoflurane, smoking and intraoperative hypotension were documented as independent risk factors for postoperative headache. In patients with no previous history of headache, caffeine consumption was an additional independent factor for postoperative headache, while smoking revealed no association.

The effect of celastrol on learning and memory in diabetic rats after sevoflurane inhalation

IntroductionThe aim was to devise an animal model showing some of the neuropathological changes seen in senile dementia, and to investigate the effect of celastrol on cognition neuropathology in this model.Material and methodsForty male Sprague Dawley rats weighing 300–350 g were randomly divided into 5 groups (n = 8 each): control (Con); inhaled sevoflurane (Sev); diabetes mellitus (DM); diabetes mellitus + inhaled sevoflurane (DM/Sev); diabetes + inhaled sevoflurane + celastrol (Cel). Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ). After 20 days, the Sev, DM/Sev and Cel group rats inhaled 3% sevoflurane for 2 h, while the control and DM groups inhaled air. Cel group rats were given intraperitoneal injections of celastrol (0.7 mg/kg) daily for 4 days, while the control group received intraperitoneal injections of an equal volume of dimethylsulfoxide. The Morris water maze test was performed to test cognition. Animals were killed after the last water maze test and Congo red staining was used to observe deposition of amyloid substance in the hippocampus. The expression of GFAP and IGF-1 in the hippocampus was observed by immunohistochemistry.ResultsDiabetes decreased cognition, increased amyloid substance and GFAP expression, and decreased IGF-1 expression in the hippocampus (all p-values < 0.05). Sevoflurane administration intensified and celastrol decreased these changes (all p-values < 0.05).ConclusionsSev/DM rats showed cognitive and neurochemical changes similar to those seen in senile dementia. Celastrol decreased these changes and should be evaluated further as a possible clinical agent in dementia.

A low dose of droperidol decreases the desflurane concentration needed during breast cancer surgery: a randomized double-blinded study.

BackgroundDroperidol (DHB) reportedly reduces the dose of propofol needed to achieve hypnosis when anesthesia is induced and decreases the bispectral index (BIS) in propofol-sedated patients during spinal anesthesia. We reported previously that supplemental DHB decreased the BIS after the administration of sevoflurane and remifentanil. This study investigated the effect of DHB on desflurane (DES) consumption in a clinical setting.MethodsWe conducted a prospective, randomized double-blinded study of 35 women with American Society of Anesthesiologist physical status I or II who underwent a mastectomy. Either DHB (20 µg/kg) or a saline placebo was administered to patients 30 min after the induction of anesthesia. A blinded anesthesiologist maintained a BIS value of 50 during anesthesia by modulating inhaled DES concentrations that changed 0.5% at 2.5 min intervals and maintained analgesia via the constant administration of remifentanil by referring to vital signs. The primary endpoint was the effect of DHB on DES consumption. The secondary endpoints included blood circulatory parameters, the time from the end of surgery to extubation, and discharge time between the groups.ResultsThe characteristics of the patients did not differ between the groups. The DHB group used a mean of 27.2 ± 6.0 ml of DES compared with 41.4 ± 9.5 ml by the placebo group (P < 0.05).ConclusionsA small dose of DHB reduced the DES concentration needed to maintain a BIS of 50. Our results show that DHB reduced the consumption of DES without adverse effects.

Comparative immunohistochemical assessment of the effect of repetitive anesthesia with isoflurane and sevoflurane on rat liver

Inhalation anesthetics are used in human, as well as veterinary medical practice. In the present study we investigated the effect of isoflurane and sevoflurane on rat hepatocytes. A total of 40 Wistar female rats were used in this study. Animals were divided in groups of 5 rats. Groups IM, SM served as control groups. Groups I1, I2, I3 were used to study isoflurane and S1, S2, S3 for sevoflurane study. They were anesthetized 3 times, for 2h long, at 2 days interval with a concentration of: 1.5% isoflurane (I1, I2, I3) and 2% sevoflurane (S1, S2, S3). The oxygen supply throughout the anesthesia was 1LO2/min. Groups IM, IS, I1, S1 were sacrificed immediately after the last anesthesia. Groups I2, S2 were sacrificed 6h after the last anesthesia, and groups I3, S3, 24h post-anesthesia. Liver samples were harvested to highlight caspase-3 in apoptotic hepatocytes. Following isoflurane administration, there were less than 1% cells in apoptosis highlighted in rat livers from groups IM, I1 and I2. At 24h post-anesthesia (group I3), a small number of apoptotic hepatocytes was highlighted (around 3.23% cells in apoptosis), with a strictly periacinar disposition, randomly distributed in a small number of hepatic lobules. After sevoflurane administration, less than 1% apoptotic hepatocytes were identified at all control moments throughout the study. The results suggest that the anesthetics do not present a considerable hepatotoxicity. The comparative assessment of the two anesthetics shows that sevoflurane is superior to isoflurane.

Analgesia Nociception Index for perioperative analgesia monitoring in spinal surgery

Background and objectivesThe Analgesia Nociception Index is an index used to measure the levels of pain, sympathetic system activity and heart rate variability during general anesthesia. In our study, Analgesia Nociception Index monitoring in two groups who had undergone spinal stabilization surgery and were administered propofol–remifentanil (Total Intravenous Anesthesia) and sevoflurane–remifentanyl anesthesia was compared regarding its significance for prediction of postoperative early pain. MethodsBIS and Analgesia Nociception Index monitoring were conducted in the patients together with standard monitoring. During induction, fentanyl 2μg.kg−1, propofol 2.5mg.kg−1 and rocuronium 0.6mg.kg−1 were administered. During maintenance, 1.0 MAC sevoflurane+remifentanil 0.05–0.3μg.kg−1.min−1 and propofol 50–150μg.kg−1.min−1+remifentanil 0.05–0.3μg.kg−1.min−1 were administered in Group S and Group T, respectively. Hemodynamic parameters, BIS and Analgesia Nociception Index values were recorded during surgery and 30min postoperatively. Postoperative visual analog scale (VAS) values at 30minutes were recorded. ResultsWhile no difference was found between mean Analgesia Nociception Index at all times of measurement in both groups, Analgesia Nociception Index measurements after administration of perioperative analgesic drug were recorded to be significantly higher compared to baseline values in both groups. There was correlation between mean values of Analgesia Nociception Index and VAS after anesthesia. ConclusionAnalgesia Nociception Index is a valuable parameter for monitoring of perioperative and postoperative analgesia. In spine surgery, similar analgesia can be provided in both Total Intravenous Anesthesia with remifentanil and sevoflurane administration. Analgesia Nociception Index is efficient for prediction of the need for analgesia during the early postoperative period, and therefore is the provision of patient comfort.

Neuroprotective effects of caffeic acid phenethyl ester against sevoflurane‑induced neuronal degeneration in the hippocampus of neonatal rats involve MAPK and PI3K/Akt signaling pathways.

Millions of infants and children are exposed to anesthesia every year during medical care. Sevoflurane is a volatile anesthetic that is frequently used for pediatric anesthesia. However, previous reports have suggested that the administration of sevoflurane promotes neurodegeneration, raising concerns regarding the safety of its usage. The present study aimed to investigate caffeic acid phenethyl ester (CAPE) and its protective effect against sevoflurane‑induced neurotoxicity in neonatal rats. Rat pups were administered with CAPE at 10, 20or 40mg/kg body weight from postnatal day1 (P1) to P15. The P7 rats were exposed to sevoflurane (2.9%) for 6h. Control group rats received no sevoflurane or CAPE. Neuronal apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick‑end labeling assay. The expression levels of caspases (caspase‑3, ‑8and ‑9), apoptotic pathway proteins [Bcl‑2‑associatedX protein (Bax), Bcell CCL/lymphoma2 (Bcl‑2), Bcl‑2‑like1 (Bcl‑xL), Bcl‑2‑associated agonist of cell death (Bad) and phosphorylated (p)‑Bad], mitogen‑activated protein kinases (MAPK) signaling pathway proteins [c‑Jun N‑terminal kinase (JNK), p‑JNK, extracellular signal‑regulated kinase (ERK)1/2, p‑ERK1/2, p38, p‑p38 and p‑c‑Jun] and the phosphoinositide 3‑kinase (PI3K)/Akt cascade were evaluated by western blotting following sevoflurane and CAPE treatment. In addition, the expression of cleaved caspase‑3 was analyzed by immunohistochemistry. CAPE significantly reduced sevoflurane‑induced apoptosis, downregulated the expression levels of caspases and pro‑apoptotic proteins (Bax and Bad) and elevated the expression levels of Bcl‑2 and Bcl‑xL when compared with sevoflurane treatment. Furthermore, CAPE appeared to modify the expression levels of MAPKs and activate the PI3K/Akt signaling pathway. Thus, the present study demonstrated that CAPE effectively inhibited sevoflurane‑induced neuroapoptosis by modulating the expression and phosphorylation of apoptotic pathway proteins and MAPKs, and by regulating the PI3K/Akt pathway.

Euthanasia using gaseous agents in laboratory rodents.

Several questions have been raised in recent years about the euthanasia of laboratory rodents. Euthanasia using inhaled agents is considered to be a suitable aesthetic method for use with a large number of animals simultaneously. Nevertheless, its aversive potential has been criticized in terms of animal welfare. The data available regarding the use of carbon dioxide (CO2), inhaled anaesthetics (such as isoflurane, sevoflurane, halothane and enflurane), as well as carbon monoxide and inert gases are discussed throughout this review. Euthanasia of fetuses and neonates is also addressed. A table listing currently available information to ease access to data regarding euthanasia techniques using gaseous agents in laboratory rodents was compiled. Regarding better animal welfare, there is currently insufficient evidence to advocate banning or replacing CO2 in the euthanasia of rodents; however, there are hints that alternative gases are more humane. The exposure to a volatile anaesthetic gas before loss of consciousness has been proposed by some scientific studies to minimize distress; however, the impact of such a measure is not clear. Areas of inconsistency within the euthanasia literature have been highlighted recently and stem from insufficient knowledge, especially regarding the advantages of the administration of isoflurane or sevoflurane over CO2, or other methods, before loss of consciousness. Alternative methods to minimize distress may include the development of techniques aimed at inducing death in the home cage of animals. Scientific outcomes have to be considered before choosing the most suitable euthanasia method to obtain the best results and accomplish the 3Rs (replacement, reduction and refinement).

General anesthesia with an injectable 8% v/v sevoflurane lipid emulsion administered intravenously to dogs

ObjectiveTo evaluate the potential of an intravenous (IV) sevoflurane formulation for maintenance of general anesthesia in dogs. Study designProspective crossover design. AnimalsSix healthy, mature, mixed-breed dogs, four males and two females, weighing 11.7 ± 3.4 kg. MethodsAnesthesia was induced and maintained with propofol IV for instrumentation. Baseline measurements were recorded before administration of either sevoflurane in oxygen (Sevo-Inh) or lipid-emulsified sevoflurane 8% v/v in 30% Intralipid IV (Sevo-E), 0.5 mL kg-1 over 5 minutes followed by an infusion at 0.1–0.3 mL kg-1 minute-1. Dogs were breathing spontaneously. The ‘up-and-down’ technique was used to determine the minimum alveolar concentration (MAC) of sevoflurane. Over 120 minutes, a tail clamp was applied every 15 minutes and sevoflurane administration was adjusted depending on the response. End-tidal sevoflurane concentration and variables were recorded at 30, 60, 90, and 120 minutes: heart rate (HR), systemic arterial pressure (sAP), respiratory rate (fR), end-tidal carbon dioxide tension, hemoglobin oxygen saturation (SaO2), arterial pH and blood gases, blood urea nitrogen, alanine aminotransferase, creatine kinase, gamma-glutamyl transferase, and aspartate aminotransferase. ResultsThere were no significant differences between treatments for HR, sAP, fR, SaO2, and biochemical variables (p > 0.05). pH and HCO3-were significantly decreased, and PaCO2 increased from baseline in Sevo-E (p < 0.05). MAC was significantly lower for Sevo-E than for Sevo-Inh, although the required dose of sevoflurane (g hour-1) to maintain general anesthesia was not significantly different between treatments. Conclusions and clinical relevanceAdministration of 8% v/v sevoflurane lipid emulsion IV was effective in maintaining general anesthesia in dogs, but resulted in moderate cardiopulmonary depression, metabolic and respiratory acidosis. The amount of sevoflurane (g hour-1) required to maintain general anesthesia was significantly lower for inhaled than for IV sevoflurane.

Life-saving Inhaled Sevoflurane Administered to an Adult With Severe Bronchospasm Secondary to COPD Exacerbation

Chronic obstructive pulmonary disease (COPD) affects over 12 million US adults, with millions more going undiagnosed. With exceedingly high levels of morbidity and mortality, it is crucial to identify rescue therapies for COPD exacerbations that are refractory to conventional therapies. Conventional therapies include supplemental oxygen, bronchodilators (β-agonists and anticholinergics), systemic corticosteroids, macrolide antibiotics, and noninvasive positive-pressure ventilation. When conventional therapies fail, rescue and salvage therapies must be considered, such as invasive mechanical ventilation, magnesium sulfate, ketamine, inhaled helium-oxygen admixture (heliox), or inhaled anesthetics. Inhaled anesthetics have long been used in the pediatric population as salvage therapy for status asthmaticus; however, there is a lack of literature to support their use in adults with severe bronchospasm due to COPD exacerbation. We present the case of a 60-year-old man who was admitted with severe COPD exacerbation, with critical bronchospasm that required mechanical ventilation after failed conventional therapies. This patient received oxygen, inhaled β-agonists and anticholingerics, intravenous corticosteroids, and macrolide antibiotics. He then required mechanical ventilation with administration of magnesium, ketamine, and inhaled heliox for his bronchospasm, with no improvement. Ultimately, he was treated successfully with an inhaled anesthetic, sevoflurane, as salvage therapy. Success was measured by decreasing peak and plateau airway pressures and a decreasing partial pressure of carbon dioxide during the administration of sevoflurane. Our case suggests an important and potential life-saving application for sevoflurane in the setting of an adult with severe bronchospasm, and larger investigations should be established to assess its role as a mainstay in rescue therapy.

Comparative immunohistochemical assessment of the effect of repetitive anesthesia with isoflurane and sevoflurane on rat liver

Background and objectivesInhalation anesthetics are used in human, as well as veterinary medical practice. In the present study we investigated the effect of isoflurane and sevoflurane on rat hepatocytes. MethodsA total of 40 Wistar female rats were used in this study. Animals were divided in groups of 5 rats. Groups IM, SM served as control groups. Groups I1, I2, I3 were used to study isoflurane and S1, S2, S3 for sevoflurane study. They were anesthetized 3 times, for 2h long, at 2 days interval with a concentration of: 1.5% isoflurane (I1, I2, I3) and 2% sevoflurane (S1, S2, S3). The oxygen supply throughout the anesthesia was 1LO2/min. Groups IM, IS, I1, S1 were sacrificed immediately after the last anesthesia. Groups I2, S2 were sacrificed 6h after the last anesthesia, and groups I3, S3, 24h post-anesthesia. Liver samples were harvested to highlight caspase-3 in apoptotic hepatocytes. ResultsFollowing isoflurane administration, there were less than 1% cells in apoptosis highlighted in rat livers from groups IM, I1 and I2. At 24h post-anesthesia (group I3), a small number of apoptotic hepatocytes was highlighted (around 3.23% cells in apoptosis), with a strictly periacinar disposition, randomly distributed in a small number of hepatic lobules. After sevoflurane administration, less than 1% apoptotic hepatocytes were identified at all control moments throughout the study. ConclusionsThe results suggest that the anesthetics do not present a considerable hepatotoxicity. The comparative assessment of the two anesthetics shows that sevoflurane is superior to isoflurane.

Relationship between Sevoflurane Plasma Concentration, Clinical Variables and Bispectral Index Values during Cardiopulmonary Bypass.

BackgroundAnesthetic administration is increasingly guided by electroencephalography (EEG)-based monitoring, such as the bispectral index (BIS). However, during cardiopulmonary bypass (CPB), factors other than the administered hypnotic agents may influence EEG signals, and their effects on BIS values are unknown.MethodsThis report is a secondary analysis of data from a prospective, controlled interventional study comparing the effect of sevoflurane administration guided by BIS monitoring (group SevoBIS) and constant administration of sevoflurane (group Sevo1.8Vol%) during CPB. Sevoflurane plasma concentration (SPC) was measured using gas chromatography. The relationships of BIS to SPC, CPB pump flow, arterial pressure, hematocrit, temperature, time on CPB, and patient characteristics were analysed.ResultsNo association was observed between BIS values and SPC in group SevoBIS. In group Sevo1.8Vol%, a 40 μg ml-1 increase in SPC, which encompassed the entire range of observed values of the SPC in this analysis, was associated with a decrease of 3.6 (95% confidence interval (CI): 1.1–6.1) in BIS values (p = 0.005). Each increase in CPB time of 10 minutes was associated with an increase in BIS values of 0.25 (95%CI: 0.11–0.39, p<0.001). Path analysis revealed that the BIS values of SevoBIS patients were 5.3 (95%CI: 3.2–7.5) units higher than those of Sevo1.8Vol% patients (p<0.001), which was the strongest effect on BIS values. Path analysis revealed a slope of 0.5 (95%CI: 0.3–0.7) BIS units per 1°C body temperature (p<0.001).ConclusionBIS monitoring is insensitive to clinically relevant changes in SPC in individual patients during CPB.

Spinal Anesthesia for Noncardiac Surgery in High-Risk Infants With Corrected Tetralogy of Fallot and Cardiomyopathy.

Dear Editor, We present a case of successful spinal anesthesia for a noncardiac surgery (NCS) featuring cardiomyopathy with corrected tetralogy of Fallot (TOF). A 29-month-old boy weighing 12.500 g, american society of anesthesiologists (ASA) physical status ІІІ required the following: bilateral orchiopexy, inguinal hernia repair, and umbilical hernia repair. He was operated on for TOF a few months ago and before the surgery we describe here, suffered from residual pulmonic stenosis and right ventricle (RV) dysfunction. The RV end-diastolic and RV end-systolic areas were high, the residual pulmonic stenosis gradient was 45 mmHg, the E/A ratio of the tricuspid valve was reversed, and regurgitation of the pulmonary valve was visible. The Doppler echocardiogram revealed that the myocardial performance index from the lateral tricuspid annulus of the right ventricle was 0.54. The patient had no other known diseases and no established condition to contraindicate for spinal anesthesia (SA). The parents were given information on SA and their written informed consent was received. In the operating room, the patient received continuous electrocardiogram, pulse oximetry, noninvasive blood pressure, and temperature monitoring. Readings were recorded every five minutes. The patient’s baseline heart rate was 127 beats.min-1, his blood pressure was 125.79 mmHg, his SpO2 was 96%, and his skin temperature was 33.2°C. Hydration was started with mixed pediatric solution (izomix 1/3 biofleks osel include 3.3 g dextrose monohydrate and 0.3 g sodium chloride per 100 g) intravenously at a rate of 5 mL/kg/s. The patient was sedated with sevoflurane in a 50% N2O - 50% O2 mixture during spontaneous breathing via a facemask. After establishing peripheral intravenous access, the patient was placed in the left lateral knee-chest position. An experienced anesthesiologist (more than 500 pediatric spinal blocks) performed a lumbar puncture at the L4-L5 interspace with a disposable 25G × 90 mm Quincke spinal needle. Sevoflurane administration was stopped after it was confirmed that the patient experienced flexia during the skin puncture. Preservative-free 0.5 mg/kg-1 of 0.5% bupivacaine was injected at a rate of 0.1 mL/s. The needle was withdrawn after maintaining it in the position for 10 seconds. Surgery was initiated after it was confirmed by pinprick that the patient did not feel pain in the inguinal area. Sensory block levels were not tested to avoid patient discomfort. Spontaneous breathing was maintained with supplementary oxygen through a facemask during the operation. Paracetamol (Parol Atabay, Turkey; include 10 mg paracetamol per 1 cc) 20 mg/kg-1 was infused during the first 20 minutes of surgery for postoperative analgesia. The patient was asleep during the procedure and did not require additional sedation. When the systolic blood pressure was decreased to 92 mmHg, an additional intravenous bolus of 25 mL of mixed solution was initiated 20 minutes after the spinal block. The surgery lasted for 40 minutes. Hypertension, tachycardia, bradycardia, hypoxemia, or apneas were not observed during surgery. The patient was awakened by tactile stimulation and then taken to the anesthesia recovery room along with his mother to ensure calm. Motor block was recovered 75 minutes after spinal block. The patient was discharged from the hospital uneventfully the day after the operation. Congenital heart diseases (CHDs) are the most prevalent group of congenital anomalies and affect approximately 79.7 per 10,000 live-born infants (1). Children with CHDs often require surgical intervention for abdominal conditions (2). The risk is greatest in neonates and infants, in whom mortality associated with NCS is two times higher in the presence of a CHD (3). Adverse events, such as cardiac arrest, bradycardia, arrhythmia, and hypotension can be predicted in infants who are less than 1-year-old, in children whose ASA physical status is high, and in patients who are endotracheally intubated and mechanically ventilated (4). For patients with cardiomyopathy, pulmonary hypertension, preoperative cyanosis, congestive heart failure, aortic stenosis, or Williams syndrome, NCS is associated with higher rates of complications than other CHDs (5). Spinal anesthesia and caudal anesthesia have a low incidence of complications and a high degree of cardiorespiratory stability (6, 7) compared with the caudal anesthesia that is commonly used in pediatric practice (7); the rapid onset of impact and the ability to easily reach high levels prompted us to choose spinal anesthesia for this patient who was scheduled for orchiopexy and umbilical hernia operations. Prior limited case reports describe the successful use of SA for NCS in pediatric patients with CHDs (5, 8, 9) and this case study further strengthens that data. This type of anesthesia should be used in children who are at high risk during general anesthesia (10). In conclusion, pediatric SA is a technique that should not be omitted when treating high-risk cardiac patients.

Effect of dexmedetomidine on the QT interval in pediatric patients undergoing general anesthesia.

Recent years have seen an increase in the use of dexmedetomidine in pediatric patients presenting for surgical procedures. However, only a limited number of studies have evaluated its effects on the QT interval in this patient group. To address this lack of knowledge, we have evaluated the effects of dexmedetomidine on the QT interval in children receiving sevoflurane anesthesia. This study was a prospective case-control study in which pediatric patients presenting for anesthetic care were divided into two groups--the dexmedetomidine (D) and control (C) groups. Three electrocardiograms (ECGs) were obtained on each patient, including a baseline ECG (T1) prior to anesthetic induction and an ECG after the induction of anesthesia with sevoflurane (T2). In group D, the third ECG was obtained 2 min after the administration of dexmedetomidine, which in turn was started immediately after the T2 ECG reading (T3D); in group C, it was obtained 2 min after the T2 reading (T3C). Statistical analysis was performed using analysis of variance to compare the QT intervals at the three time points outlined above. A total of 50 patients were recruited to the study, ranging in age from 1 to 16 [mean 7.9 ± 4.1 (SD) years]. There were 25 patients in group C and 25 in group D. There were no statistical differences in the demographics between the 2 groups. In group C, the QTc was noted to increase progressively with the administration of sevoflurane (T3C vs. T1; P = 0.006). In group D, following the administration of dexmedetomidine, there was a significant decrease in the QTc relative to the post-induction value [436 ± 25 (T2) vs. 418 ± 17 ms (T3D); P < 0.01]. A progressive lengthening of the QTc interval following the administration of sevoflurane was observed in the control group. In the dexmedetomidine group, there was a significant shortening of the QTc interval following the administration of dexmedetomidine compared to the length of the post-induction QTc interval and when compared to the control group.

Experimental Ex Vivo Lung Perfusion with Sevoflurane: Effect on donors after circulatory death (DCD) lung grafts in a rodent model.

Ischemia-reperfusion injury is a key mechanism of graft damage during lung transplantation, which could be targeted by therapies applied during ex-vivo lung perfusion (EVLP). The inhalational anaesthetic Sevoflurane was found to protect to some degree against ischemia-reperfusion injury1. In this experimental study we wanted to determine the therapeutic potential of volatile Sevoflurane added to the perfusate during EVLP of damaged lung grafts. Two groups of 6 Sprague-Dawley rats were used. After cardiac arrest and a warm ischemic time of 1 hour the lungs were flushed with cold Perfadex®, harvested and kept for 2 hours at 4°C. Normothermic EVLP during 3 hours was performed using a customized circuit primed either with Steen solution® only (control group) or supplemented within the first 30 minutes of EVLP with a gas mixture containing 2% of sevoflurane (treatment group). Differential oxygen partial pressures in the perfusate (ΔvapO2), pulmonary artery pressure (PAP), vascular resistance (PVR), lung compliance (LC), peak airway pressure (PAWP) and lung weight gain (WG) were measured. At the end of EVLP, protein and lactate dehydrogenase (LDH) levels were determined in bronchoalveolar lavage (BAL) and interleukin-6 (IL-6) and protein carbonyl (index of oxidative stress) were measured in lung tissue. Normothermic EVLP of lungs harvested after warm ischemia resulted in markedly declined ΔvapO2, LC, and elevated PAP, PVR, PAWP, WG. In contrast, lungs treated with Sevoflurane during EVLP displayed significantly improved LC, reduced weight gain and significantly lower LDH and protein carbonyl levels as compared to controls. PAWP and IL-6 were diminished in treated lungs, but were not statistically different to controls. The intravascular administration of sevoflurane during EVLP reduces oxidative stress and improves the functional status of DCD rat lungs in this experimental setting.

Elevation of Sestrin-2 expression attenuates Sevoflurane induced neurotoxicity.

Sevoflurane, one of the most commonly used volatile anesthetics in clinical treatment, has been shown to induce a widespread increase in brain apoptosis. However, the underlying mechanism is still unknown. Sestrin 2 has been recently shown to regulate intracellular reactive oxygen species (ROS) levels and play a crucial role in p53-dependent antioxidant defenses. In this study, our results indicated that administration of Sevoflurane elevated the gene and protein expression of Sestrin-2 in a dose dependent manner in human neuroblastoma M17 cells. It was shown that silence of Sestrin-2 by small RNA interference (siRNA) ominously exacerbated the increase in intracellular ROS and reduction of SOD activity induced by Sevoflurane treatment. Notably, knockdown of Sestrin-2 in M17 cells significantly increases the number of apoptotic cells after treatment with Sevoflurane. Mechanistically, we also found that Sevoflurane treatment resulted in a reduced amount of the cytosolic anti-apoptotic protein Bcl-2 but an increased amount of Bax, which was exacerbated by knockdown of Sestrin-2. In addition, knockdown of Sestrin-2 remarkably increased the elevated cleaved Caspase-3 expression. Finally, we showed that the induction of Sestrin-2 by Sevoflurane was mediated by p53. These results suggest that the suppressive effects of Sestrin-2 on neuroapoptosis against the Sevoflurane anesthesia in neuronal cells might be associated with modulation of mitochondrial pathway.

Effect of ramosetron on the QT interval during sevoflurane anaesthesia in children

We investigated the effects of concomitant administration of sevoflurane and ramosetron on the QT interval, the interval between the peak and end of the T wave (Tpe) and Tpe/QT ratio in children. To compare the effects of concomitant administration of ramosetron and sevoflurane on heart rate corrected interval with Bazett's formula (QTc), Tpe interval and Tpe/QT ratio. A prospective observational study. Elective orthopaedic surgery with patient-controlled analgesia. Forty children aged between 3 and 12 years. ECG recordings were collected before induction (BASE), before sevoflurane administration (SEVO) and after the administration of ramosetron (SEVO and R). The heart rate corrected interval with Bazett's formula (QTc), Tpe interval and Tpe/QT ratio were calculated and the changes were analysed using repeated-measures analysis of variance (ANOVA). The QTc interval at BASE was 388.5 ± 29.3 ms. It increased with sevoflurane anaesthesia to 414.9 ± 21.4 ms and did not change with the administration of ramosetron (418.2 ± 23.0 ms). The Tpe interval and Tpe/QT ratio did not differ between measurements. No ventricular arrhythmias occurred during the study. Ramosetron was not associated with prolongation of the QTc interval when it was given concomitantly with sevoflurane in children. No ventricular arrhythmias or other adverse effects occurred during the study.

Renal and hepatic integrity in long-term sevoflurane sedation using the anesthetic conserving device: A comparison with intravenous propofol sedation in an animal model

IntroductionCritically ill patients are sedated with intravenous agents because the use of inhaled agents is limited by their potential risk of toxicity. Increasing levels of inorganic fluorides after the metabolism of these agents have been considered potentially nephrotoxic. However, hepatic involvement after prolonged administration of sevoflurane has not yet been studied. The present study evaluated the potential renal and hepatic toxicity caused by prolonged administration (72h) of sevoflurane. MethodsFor this experimental, prospective, randomized, controlled trial, 22 Landrace×Large-White female pigs were randomly assigned to two groups: intravenous propofol (P) or inhaled sevoflurane via the AnaConDa™ device (S, end-tidal 2.5vol%). The P group remained sedated for 108h with propofol. In the S group, sevoflurane was administered for 72h and then changed to propofol for the remaining 36h in order to observe the kinetics of fluoride after discontinuation of sevoflurane. Serum creatinine was the primary outcome variable, but inorganic fluoride concentrations and other renal, hepatic, and cardiorespiratory variables were also measured. ResultsBoth groups of animals were comparable at baseline. No differences were found between the two groups for plasma creatinine and urea or creatinine clearance throughout the study. Fluoride levels were significantly higher in the sevoflurane group. No correlation was found between inorganic fluoride and serum creatinine values. No significant differences were observed for hepatic function. Hemodynamic, respiratory, and blood gas variables were comparable between the groups. ConclusionsLong-term sedation with sevoflurane using AnaConDa™ or propofol does not negatively affect renal or hepatic function.

Hepatic cytoprotective effect of ischemic and anesthetic preconditioning before liver resection when using intermittent vascular inflow occlusion: A randomized clinical trial

Ischemic preconditioning (IPC) and anesthetic preconditioning (APC) have been reported to attenuate ischemia-reperfusion (IR) injury after liver resection under continuous inflow occlusion. This study evaluates whether these strategies enhance hepatic protection of remnant liver against IR after liver resection with intermittent clamping (INT). A total of 106 patients without underlying liver disease and submitted to liver resection using INT were randomized into 3 groups: IPC (10 minutes of inflow occlusion followed by 10 minutes of reperfusion before liver transection), APC (sevoflurane administration for 20 minutes before liver transection), and INT (no preconditioning). Patients were also stratified according to the extent of the hepatectomy. Cytoprotection was evaluated by comparing hepatocyte and endothelial dysfunction markers, apoptosis, histologic lesions, and postoperative outcome. No differences were observed in preoperative chemotherapy and steatosis, total warm ischemia time, operative time, or blood loss. Kinetics of transaminases (aspartate aminotransferase, P = .137; alanine aminotransferase, P = .616), bilirubin (P = .980), and hyaluronic acid increase (P = .514) revealed no differences. Significant apoptosis was present in 40% of patients, mild-to-moderate leukocyte infiltration and steatosis in 45% and 55%, respectively, and mild sinusoidal congestion in 65%, with a similar distribution in the 3 groups. When patients were stratified by major versus minor resections, no differences were observed in any of the variables studied. Postoperative clinical outcomes were also similar. These results suggest that these protocols of IPC and APC used in this study do not provide better cytoprotection from IR when INT is used.

Sevoflurane attenuates stress-enhanced fear learning by regulating hippocampal BDNF expression and Akt/GSK-3β signaling pathway in a rat model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disease that may occur after intense psychological trauma or physiological stress. Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) and the serine/threonine kinase (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway are critically involved in brain plasticity, including hippocampal-dependent learning and memory, while sevoflurane impairs memory processing. Thus, we hypothesized that sevoflurane can suppress fear learning by regulating the expression of BDNF and the Akt/GSK-3β signaling pathway in a rat model of PTSD. Rats were exposed to sevoflurane during or after a 15 foot-shock stressor. Thereafter, rats were subjected to a single foot-shock in a totally different environment. The fear response was recorded in response to the 15 foot-shock and the single foot-shock environments. In another set of experiments, the brain tissue was harvested and subjected to biochemistry studies. Our data suggested that increasing sevoflurane concentrations decreased stress-enhanced fear learning (SEFL) when given during but not after the stressor. Furthermore, administration of lithium chloride (100 mg/kg, intraperitoneally) 30 min before the contextual fear conditioning reversed the inhibitory effect of 0.8 % sevoflurane on SEFL as well as phosphorylated (p)-Akt, p-GSK-3β and BDNF expressions. Our data suggested that increasing sevoflurane administration during but not after the stressor can impair SEFL in a rat model of PTSD, which may be due, at least in part, to the regulation of hippocampal BDNF expression and the Akt/GSK-3β signaling pathway.

A combination of mild hypothermia and sevoflurane affords long-term protection in a modified neonatal mouse model of cerebral hypoxia-ischemia.

Infant brain injury from hypoxia-ischemia (HI) can lead to life-long impairment, but protective strategies are lacking. Short-term but not long-term protection has been demonstrated in the Rice-Vannucci neonatal brain ischemia model (RVM) by volatile anesthetic administration before HI, while exposure during HI has not been tested. In the current study, we evaluated a combination of sevoflurane and mild hypothermia as a protective approach during HI, both short- and long-term, by introducing intubation and mechanical ventilation to the RVM. The right common carotid artery was ligated in 10-day-old mice during brief sevoflurane anesthesia, followed by a 2-hour recovery with the dam. Littermates were then randomized to either: HI spontaneously breathing 10% oxygen for 60 minutes (the classical RVM); HI-Protect mild hypothermia and orotracheal intubation and mechanical ventilation with 3.5% sevoflurane in 10% oxygen for 60 minutes; or Room Air spontaneously breathing room air for 60 minutes. In a nonsurviving cohort, cerebral oxygenation was monitored in the area at risk and the contralateral hemisphere during HI or HI-Protect using visible-light spectroscopy (Spectros Corp). Mean arterial blood pressure and heart rate were measured. Arterial blood gases were obtained. Right/left brain hemispheric weight ratios and brain damage scores were determined 1 week after HI. In another group, learning and behavior were assessed in young adulthood (9 weeks) using spontaneous locomotion, Morris water maze, and apomorphine injection. During HI, ipsilateral and contralateral brain oxygenation, arterial blood pressures, blood gases, and glucose levels were similar in both ischemic groups, while heart rate was slower in the HI-Protect group. One week after ischemia, brain hemispheric weight ratios and injury scores in several brain regions were significantly worse after HI, compared with HI-Protect. Nine weeks after HI, Morris water maze hidden platform and reversal platform escape latencies, measures of spatial memory function, were superior after HI-Protect, compared with HI (P < 0.0001). HI-Protect animals demonstrated significantly less circling behavior after an apomorphine challenge (P < 0.0001), a measure of striatal integrity. To test the neuroprotective effects of volatile anesthetics during neonatal brain ischemia, we developed a modification of the RVM. By using mechanical ventilation and endotracheal intubation, sevoflurane administration during HI was survivable. The combination of sevoflurane administration and mild hypothermia during HI conferred not only short-term structural, but also long-term functional protection, compared with littermates treated according to the RVM. These findings warrant further studies to improve neurological outcome in critically ill infants.