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1.  Comparison of hepatic and renal function between inhalation anesthesia with sevoflurane and remifentanil and total intravenous anesthesia with propofol and remifentanil for thyroidectomy 
Korean Journal of Anesthesiology  2013;64(2):112-116.
Inhalation anesthetics are an important factor for postoperative hepatic and renal dysfunction. In this regard, TIVA can reduce the risk of hepatic and renal dysfunction inherited to inhalation anesthetics. The present study was conducted to determine whether hepatic and renal functions differ after anesthesia with sevoflurane and propofol.
Two hundred patients, ASA physical status class I, II, scheduled for an elective thyroidectomy were randomly divided into two groups. Anesthesia was maintained with sevoflurane 1-2% and remifentanil in the sevoflurane group (Group S) and propofol 2-5 ug/ml and remifentanil 2-5 ng/ml at the effect site, using a target controlled infusion (TCI) pump in the TIVA group (Group T) to maintain BIS of 40-60. To evaluate the hepatic and renal function, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine were tested at preoperation (baseline), postoperative 1 day and 3 days.
AST was increased at postoperative 1 day and 3 days, compared with that of the preoperation in Group S, and postoperative 1 day in Group T, but the values were within its normal limit. ALT was not changed after anesthesia in both groups. BUN was increased at postoperative 1 day, compared with that of the preoperation in Group S, but the value was within its normal limit. Creatinine was not changed after anesthesia in both groups.
The changes of hepatic and renal function after inhalation anesthesia with sevoflurane and TIVA with propofol and remifentanil for thyroidectomy were clinically insignificant, and there was no difference between the two methods.
PMCID: PMC3581778  PMID: 23459368
Alanine aminotransferase; Aspartate aminotransferase; Blood Urea Nitrogen (BUN); Creatinine; Inhalation anesthesia; Total intravenous anesthesia
2.  Effects of repeat exposure to inhalation anesthetics on liver and renal function 
Cross hypersensitivity to inhalation anesthetics has not been studied. The aim of this study was to investigate it by comparing liver and renal function after repeated anesthesia with sevoflurane and isoflurane retrospectively.
Materials and Methods:
The adult patients who received general anesthesia twice within the interval of 14 days to 1 year were retrospectively analyzed. Those who received sevoflurane anesthesia twice (SS group, 53 cases), isoflurane anesthesia twice (II group, 31 cases), sevoflurane followed by isoflurane anesthesia (SI group, 29 cases), isoflurane followed by sevoflurane anesthesia (IS group, 35 cases), and propofol–fentanyl anesthesia twice (PP group, 58 cases) were enrolled. Serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (Bil), gamma-glutamyl transpeptidase (γ-GTP), blood urea nitrogen (BUN), and creatinine (Cr) measured 1-3, 5-8, and 12-16 days after surgery were investigated.
In the IS group, the number of the patients with abnormal values of ALT and γ-GTP 5–8 days after surgery were significantly smaller at second anesthesia compared to the first anesthesia. The number of the patients with abnormal values of AST, ALT, and γ-GTP were significantly larger in the II group than the SS and PP groups. The number of patients who had higher values in each parameter at second anesthesia compared to the first anesthesia was not different among the groups.
Sevoflurane and isoflurane might have no cross hypersensitivity. Both anesthetics might not have any additional risks to increase liver and renal damage by second anesthesia.
PMCID: PMC3590549  PMID: 23493664
General anesthesia; isoflurane; kidney; liver; propofol; sevoflurane
Liver Transplantation  2012;18(2):166-176.
Early allograft dysfunction (EAD) occurring in the first week post-liver transplantation is associated with increased graft failure and mortality and is believed to be largely due to ischemia/reperfusion injury. We anticipated that the presence of EAD would be reflected by alterations in expression of serum proteins associated with an inflammatory response in the peri-operative period, and hypothesized that a specific pattern of expression might correlate with the development of EAD. The serum levels of 25 cytokines, chemokines, and immunoreceptors were measured by Luminex multiplex assays pre- and post-liver transplantation. Levels of each cytokine biomarker were compared in adult recipients with or without EAD at serial time points using samples collected pre-operatively and at 1, 7, 14, and 30 days post-transplant. EAD was defined according to standard criteria as maximum alanine transferase (ALT) or aspartate transferase (AST) levels on days 1–7 of >2000 U/ml, day 7 bilirubin level ≥10 mg/dl, or a day 7 international normalized ratio (INR) ≥1.7. Multivariable analyses showed that patients experiencing EAD had lower pre-operative IL-6 and higher IL-2R levels. Patients with EAD also showed higher MCP-1 (CCL2), IL-8 (CXCL8), and RANTES (CCL5) chemokine levels in the early post-operative period, suggesting up-regulation of the NF-κB pathway, in addition to higher levels of chemokines and cytokines associated with T cell immunity, including Mig (CXCL9), IP-10 (CXCL10) and IL-2R. These findings identify several possible biomarkers and pathways associated with EAD, that may guide future validation studies and investigation of specific cellular and molecular mechanisms of graft dysfunction. Furthermore, if validated, our findings may contribute to perioperative prediction of the occurrence of EAD and ultimately lead to identification of potential interventional therapies.
PMCID: PMC3266982  PMID: 22006860
immune monitoring; multiplex analysis; chemokines; immunobiology
4.  Effects of sevoflurane preconditioning and postconditioning on rat myocardial stunning in ischemic reperfusion injury*  
Ischemic preconditioning and postconditioning distinctly attenuate ventricular arrhythmia after ischemia without affecting the severity of myocardial stunning. Therefore, we report the effects of sevoflurane preconditioning and postconditioning on stunned myocardium in isolated rat hearts. Isolated rat hearts were underwent 20 min of global ischemia and 40 min of reperfusion. After an equilibration period (20 min), the hearts in the preconditioning group were exposed to sevoflurane for 5 min and next washout for 5 min before ischemia. Hearts in the sevoflurane postconditioning group underwent equilibration and ischemia, followed immediately by sevoflurane exposure for the first 5 min of reperfusion. The control group received no treatment before and after ischemia. Left ventricular pressure, heart rate, coronary flow, electrocardiogram, and tissue histology were measured as variables of ventricular function and cellular injury, respectively. There was no significant difference in the duration of reperfusion ventricular arrhythmias between control and sevoflurane preconditioning group (P=0.195). The duration of reperfusion ventricular arrhythmias in the sevoflurane postconditioning group was significantly shorter than that in the other two groups (P<0.05). ±(dP/dt)max in the sevoflurane preconditioning group at 5, 10, 15, 20, and 30 min after reperfusion was significantly higher than that in the control group (P<0.05), and there were no significant differences at 40 min after reperfusion among the three groups (P>0.05). As expected, for a 20-min general ischemia, infarct size in heart slices determined by 2,3,5-triphenyltetrazolium chloride staining among the groups was not obvious. Sevoflurane postconditioning reduces reperfusion arrhythmias without affecting the severity of myocardial stunning. In contrast, sevoflurane preconditioning has no beneficial effects on reperfusion arrhythmias, but it is in favor of improving ventricular function and recovering myocardial stunning. Sevoflurane preconditioning and postconditioning may be useful for correcting the stunned myocardium.
PMCID: PMC2852543  PMID: 20349523
Inhalation anesthetics; Sevoflurane; Postconditioning; Preconditioning; Ischemia-reperfusion injury; Myocardial stunning
5.  Effect of sevoflurane on grafted kidney function in renal transplantation 
Korean Journal of Anesthesiology  2012;62(6):529-535.
The objective of this retrospective study was to determine if there are any differences in grafted kidney function in recipients of kidney transplantation (KT) when donors and recipients were anesthetized with sevoflurane compared to desflurane.
Seventy-three pairs of donors-recipients were anesthetized with sevoflurane (Sevo group) and 71 pairs were anesthetized with desflurane (Des group). We retrospectively investigated the blood urea nitrogen (BUN) levels, creatinine (Cr) levels, and estimated glomerular filtration rates (eGFR) of the recipients in both groups for 1 year postoperatively. We tested non-inferiority for serum creatinine at discharge and 1 year after KT. Short-term (1 year) outcomes of KT were assessed by the incidence of delayed graft function (DGF), acute rejection episodes (ARE), and graft failure.
There were no differences in BUN, Cr, eGFR, or outcomes of KT at 1 year postoperatively. Specifically, the 95% confidence interval for the difference in creatinine levels between the Sevo and Des groups was less than the margin of equivalence at the time of discharge and 1 year after surgery. The occurrences of DGF, ARE, and graft failure were comparable between the groups.
Compared to desflurane, sevoflurane had no adverse effects on grafted renal function or on the short-term outcome of renal transplantation.
PMCID: PMC3384790  PMID: 22778888
Creatinine; Glomerular filtration rate; Kidney transplantation; Sevoflurane
6.  The effects of hydrogen sulfide under sevoflurane administration against ischemia and reperfusion injury in isolated rat heart 
Korean Journal of Anesthesiology  2012;62(5):461-467.
Hydrogen sulfide (H2S) produces a protective effect against myocardial ischemia and reperfusion injury. Sevoflurane, which is used for anesthesia in cardiac problem patients, also has a protective effect. This study is designed to reveal the effects of H2S under sevoflurane using rat hearts.
The hearts were Langendorff-perfused, subjected to 30 minutes ischemia and 60 minutes reperfusion. Group I was a control group. The other groups were pretreated for 15 minutes before ischemia as follows: 1.6% sevoflurane for group S; 18.5 µM H2S S for group H; and 1.6% sevoflurane and 18.5 µM H2S simultaneously for group HS. Hemodynamics and the infarct size were measured.
Group HS presented depressed hemodynamics during pretreatment. LV function in group HS achieved better recovery than group I after reperfusion. The infarct size of groups S, H and HS was smaller than group I, while there were no differences between groups S, H and HS.
Exogenous H2S did not enhance the preconditioning effects of sevoflurane. Rather, the results suggest that H2S under sevoflurane might depress hemodynamics.
PMCID: PMC3366314  PMID: 22679544
Heart; Hydrogen sulfide; In vitro; Ischemia; Reperfusion injury; Sevoflurane
7.  Sedation with sevoflurane in postoperative cardiac surgery: influence on troponin T and creatinine values 
Heart, Lung and Vessels  2014;6(1):33-42.
To compare the potential beneficial effects on markers of myocardial injury (troponin T) and renal function between sedation with sevoflurane vs propofol after cardiac surgery using extracorporeal cardiopulmonary bypass.
A prospective study with sequential selection of patients undergoing coronary or coronary and valve cardiac surgery. Intraoperative anesthesia consisted in sevoflurane and remifentanil, while in the postoperative period patients were divided in two groups to receive sedation with either sevoflurane through the AnaConDa© system or propofol. The patients were sedated during a minimum of 120minutes. Markers of myocardial injury and plasmatic creatinine were measured 4, 12, 24, and 48hours after surgery.
Data from 129patients, 62sedated with propofol and 67with sevoflurane, were analyzed. The analysis of the troponin T levels showed differences 12 and 48 hours after admission. Mean values at 12hours were 0.89 (standard deviation 0.55) µg.L-1 in the propofol group and 0.69 (standard deviation 0.40) µg. L-1in the sevoflurane group (p = 0.026). TnT levels at 48hours were 0.60 (standard deviation 0.46) µg.L-1in the propofol group and 0.37 (standard deviation 0.26) µg.L-1in the sevoflurane group (p = 0,007). No differences were found in the groups in the creatinine levels before discharge.
The post-operative sedation with sevoflurane after cardiac surgery with cardiopulmonary bypass is a valid alternative to propofol. It does not increase the number of side effects related to kidney damage in patients with no prior renal disease, leading to reduced troponin T levels 12and 48hours after admission.
PMCID: PMC4009595  PMID: 24800196
sedation; cardiac surgery; postoperative care; sevoflurane; propofol
8.  Cognitive dysfunction following desflurane versus sevoflurane general anesthesia in elderly patients: a randomized controlled trial 
As life expectancy increases, more patients ≥65 years undergo general anesthesia. Anesthetic agents may contribute to postoperative cognitive dysfunction, and incidence may differ with anesthetic agents or intraoperative anesthesia depth. Responses to anesthetic adjuvants vary among elderly patients. Processed electroencephalography guidance of anesthetic may better ensure equivalent cerebral suppression. This study investigates postoperative cognitive dysfunction differences in elderly patients given desflurane or sevoflurane using processed electroencephalography guidance.
IRB approved, randomized trial enrolled consenting patients ≥65 years scheduled for elective surgery requiring general anesthesia ≥120 minute duration. After written informed consent, patients were randomly assigned to sevoflurane or desflurane. No perioperative benzodiazepines were administered. Cognitive impairment was measured by an investigator blinded to group assignment using mini-Mental Status Examination (MMSE) at baseline; 1, 6, and 24 hours after the end of anesthesia. Mean arterial pressure was maintained within 20% of baseline. Anesthetic dose was adjusted to maintain moderate general anesthesia per processed electroencephalograpy (Patient State Index 25 to 50). The primary outcome measure was intergroup difference in MMSE change 1 hour after anesthesia (median; 95% confidence interval).
110 patients consented; 26 were not included for analysis (no general anesthesia; withdrew consent; baseline MMSE abnormality; inability to perform postoperative MMSE; data capture failure); 47 sevoflurane and 37 desflurane were analyzed. There were no significant differences in patient characteristics; intraoperative mean blood pressure (desflurane 86.4; 81.3 to 89.6 versus sevoflurane 82.5; 80.2 to 86.1 mmHg; p = 0.42) or Patient State Index (desflurane 41.9; 39.0 to 44.0 versus sevoflurane 41.0; 37.5 to 44.0; p = 0.60) despite a lower MAC fraction in desflurane (0.82; 0.77 to 0.86) versus sevoflurane (0.96; 0.91 to 1.03; p < 0.001). MMSE decreased 1 hour after anesthesia (p < 0.001). The decrease at one hour was larger in sevoflurane (−2.5; −3.3 to −1.8) than desflurane (−1.3; −2.2 to −0.5; p = 0.03). MMSE returned to baseline by 6 hours after anesthesia.
For elderly patients in whom depth of anesthesia is maintained in the moderate range, both desflurane and sevoflurane are associated with transient decreases in cognitive function as measured by MMSE after anesthesia, with clinically insignificant differences between them in this setting.
Trial registry NCT01199913
PMCID: PMC3976084  PMID: 24666542
General anesthesia; Postoperative cognitive decline; Geriatric patient
9.  Kidney Function in Living Donors Undergoing Nephrectomy by Sevoflurane or Desflurane Anesthesia 
Yonsei Medical Journal  2013;54(5):1266-1272.
Although there is no clinical evidence of nephrotoxicity with the volatile anesthetics currently used in general anesthesia, a better agent should be needed in terms of preserving postoperative renal function in living kidney donors who have only single remaining kidney. The purpose of the current retrospective, single-center study was to evaluate and compare renal function of living kidney donors after nephrectomy under either sevoflurane or desflurane anesthesia.
Materials and Methods
From January 2006 through December 2011, a total of 228 donors undergoing video assisted minilaparotomy surgery nephrectomy for kidney donation were retrospectively enrolled in the current study. The donors were categorized into a sevoflurane group or desflurane group based on the type of volatile anesthetic used. We collected laboratory data from the patients preoperatively, immediately after the operation, on the first postoperative day and on the third postoperative day. We also compared renal function of the kidney donors after donor nephrectomy by comparing creatinine level and estimated glomerular filtration rate (eGFR).
The decrease in renal function after surgery in both groups was the most prominent on the first postoperative day. There were no significant differences between the two groups in postoperative changes of creatinine or eGFR.
Sevoflurane and desflurane can be used safely as volatile anesthetics in donors undergoing nephrectomy.
PMCID: PMC3743197  PMID: 23918580
Desflurane; living donors; nephrectomy; sevoflurane
10.  Volatile anaesthetic myocardial protection: a review of the current literature 
Ischaemic preconditioning is a powerful innate adaptive phenomenon whereby brief periods of sublethal ischaemia result in marked tolerance to subsequent lethal ischaemia. Halogenated anaesthetics have been shown to mimic ischaemic preconditioning, modifying and attenuating ischaemia reperfusion injury.
This review aims to present the current animal and human data, discuss the possible mechanisms of action and review the clinical evidence for volatile anaesthetic-induced myocardial protection.
There is class Ia evidence for the myocardial protective properties of sevoflurane and desflurane in low risk patients undergoing coronary artery bypass grafting surgery.
These volatile anaesthetics have been shown to improve clinical outcomes and health economics following cardiac surgery, reducing intensive care and hospital stay. The evidence for the benefit of volatile anaesthetics in non-cardiac surgery is less robust and further large randomized controlled trials are required to elucidate this question.
PMCID: PMC3484611  PMID: 23440181
volatile anaesthetics; myocardial protection; ischaemic preconditioning; mechanisms; cardiac anaesthesia; outcomes
11.  Anesthesia with Propofol versus Sevoflurane: Does the Longer Neuromuscular Block under Sevoflurane Anesthesia Reduce Laryngeal Injuries? 
Anesthesia can be maintained with propofol or sevoflurane. Volatile anesthetics increase neuromuscular block of muscle relaxants. We tested the hypothesis, that sevoflurane would cause less vocal cord injuries than an intravenous anesthesia with propofol. In this prospective trial, 65 patients were randomized in 2 groups: SEVO group, anesthesia with sevoflurane, and TIVA group, total intravenous anesthesia with propofol. Intubating and extubating conditions were evaluated. Vocal cord injuries were examined by stroboscopy before and 24 and 72 h after surgery; hoarseness and sore throat were assessed up to 72 h after surgery. Hoarseness and sore throat were comparable between both groups (not significant). Similar findings were observed for vocal cord injuries: 9 (SEVO) versus 5 (TIVA) patients; P = 0.36; the overall incidence was 24%. Type of vocal cord injuries: 9 erythema and 5 edema of the vocal folds. Neuromuscular block was significantly longer in the SEVO group compared with the TIVA group: 71 (range: 38–148) min versus 52 (range: 21–74) min; P < 0.001. Five patients (TIVA group) versus 11 patients (SEVO group) needed neostigmine to achieve a TOF ratio of 1.0 (P = 0.14). Under anesthesia with propofol laryngeal injuries were not increased; the risk for residual curarization, however, was lower compared with sevoflurane.
PMCID: PMC3600211  PMID: 23533393
12.  The Comparison of the Effects of Sevoflurane Inhalation Anesthesia and Intravenous Propofol Anesthesia on Oxidative Stress in One Lung Ventilation 
BioMed Research International  2014;2014:360936.
Background. The aim of this study is to compare the effects of sevoflurane and propofol on one lung ventilation (OLV) induced ischemia-reperfusion injury (IRI) by determining the blood gas, ischemia-modified albumin (IMA), and malonyldialdehyde (MDA). Material and Methods. Forty-four patients undergoing thoracic surgery with OLV were randomized in two groups (sevoflurane Group S, propofol Group P). Anesthesia was inducted with thiopental and was maintained with 1–2.5% of sevoflurane within the 40/60% of O2/N2O mixture in Group S. In Group P anesthesia was inducted with propofol and was maintained with infusion of propofol and remifentanil. Hemodynamic records and blood samples were obtained before anesthesia induction (t1), 1 min before two lung ventilation (t2), 30 min after two lung ventilation (t3), and postoperative sixth hours (t4). Results. Heart rate at t2 and t3 in Group P was significantly lower than that in Group S. While there were no significant differences in terms of pH and pCO2, pO2 at t2 and t3 in Group S was significantly lower than that in Group P. IMA levels at t4 in Group S were significantly lower than those in Group P. Conclusion. Sevoflurane may offer protection against IRI after OLV in thoracic surgery.
PMCID: PMC3909970  PMID: 24527444
13.  The effect of a subhypnotic dose of propofol for the prevention of coughing in adults during emergence from anesthesia with sevoflurane and remifentanil 
Korean Journal of Anesthesiology  2014;66(2):120-126.
Coughing during emergence from general anesthesia may be detrimental. Propofol is known to inhibit airway reflexes. We evaluated the incidence and severity of coughing in adults who received a subhypnotic dose of propofol at the end of sevoflurane-remifentanil anesthesia.
Sixty patients, aged 18-65 years, undergoing elective nasal surgery under general anesthesia using sevoflurane and remifentanil were randomly allocated to the propofol group (n = 30) or the control group (n = 30). At the end of surgery, sevoflurane and remifentanil infusion was stopped. After 3 min, the propofol group received propofol 0.3 mg/kg and the control group received normal saline 0.03 ml/kg. The incidence and severity of cough, recovery time and hemodynamic parameters were evaluated during the emergence period.
During emergence, the propofol group had the significantly lower incidence (60 vs. 87%) and severity of coughing compared with the control group (P = 0.04, P = 0.02, respectively). There were no significant differences in mean arterial pressure, heart rate, and recovery time during emergence between the two groups.
During emergence from sevoflurane-remifentanil anesthesia, a subhypnotic dose (0.3 mg/kg) of propofol decreases the incidence and severity of coughing without delaying wake up in adults undergoing nasal surgery.
PMCID: PMC3948438  PMID: 24624269
Cough; Emergence; Propofol
14.  Early Cardioprotective Effect of Sevoflurane on Left Ventricular Performance during Coronary Artery Bypass Grafting on a Beating Heart: Randomized Controlled Study 
Croatian medical journal  2007;48(3):333-340.
To evaluate the cardioprotective effect of sevoflurane on a beating heart in patients undergoing coronary artery bypass grafting with normal preoperative left ventricular function.
The randomized controlled study included 32 patients induced with sevoflurane and then randomized to receive either 1 minimal alveolar concentration (MAC) end-tidal concentration of sevoflurane (n = 16) or propofol (n = 16) 2 to 3 mg kg-1 hour-1. The acceleration of the aortic blood flow, cardiac index, heart rate, mean arterial pressure, and central venous pressure were measured 5 minutes after anesthesia induction, at the beginning of ischemia, 15 minutes after ischemia, and 15 minutes after sternum closure.
There were no differences in heart rate, mean arterial pressure, and central venous pressure within each group and between groups during surgery. Acceleration increased in the sevoflurane group 15 minutes after ischemia (10.3 ± 3.5 m/s2; P = 0.004) and 15 minutes after sternum closure (10.7 ± 3.9 m/s2; P<0.001). Acceleration in the propofol group decreased from the beginning of ischemia (P<0.001) and remained lower 15 minutes after sternum closure (P = 0.001 and P = 0.024, respectively). Acceleration was higher in the sevoflurane group at the beginning of ischemia and 15 minutes after sternum closure (P = 0.017 and P = 0.046, respectively). There were no significant differences in cardiac index values within the sevoflurane group. In the propofol group, significant decreases in cardiac index were seen at the beginning of ischemia (P<0.001). There were between-group differences in cardiac index values at the beginning of ischemia and 15 minutes after ischemia (P = 0.002, and P = 0.011, respectively).
Cardiac function was better preserved in the patients anesthetized with sevoflurane than in patients anesthetized with propofol.
Trial Registration Identifier
PMCID: PMC2080533  PMID: 17589976
15.  Inhalation induction with sevoflurane in adult cardiac surgery patients. A case series 
Heart, Lung and Vessels  2014;6(1):8-12.
Anesthesia induction through volatile agents is a well-established technique in several fields but not in adult patients undergoing cardiac surgery. Successful inhalation induction requires a poorly soluble, reasonably potent and minimally irritant agent, and the benefits associated to this technique include reduced incidence of hypothermia and hypotension and lower costs when compared to some intravenous anesthetics agents.
Fifty-six patients undergoing coronary artery bypass grafting were observed at the induction of general anesthesia with sevoflurane in oxygen by facial mask. All patients received 2% sevoflurane in 100% oxygen initially for 30 seconds. The inspired concentration of sevoflurane was increased to 7% until loss of consciousness and then reduced back to 2%. Next, intravenous 0.5 µg/kg sufentanil and 0.1 mg/kg pancuronium were administered. Volume-controlled ventilation was started before tracheal intubation.
All 56 patients tolerated the inhalational induction. No patient presented signs of airway irritation. Hypotension occurred in 30 patients and was managed with low dose phenylephrine.
This case series showed that inhalation induction is feasible and safe even in adult patients undergoing cardiac surgery.
PMCID: PMC4009592  PMID: 24800193
volatile anesthetics; sevoflurane; anesthetics technique; induction; cardiac surgery
16.  Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in mice 
Mechanical ventilation has been documented to paradoxically cause lung injury. As a commonly used volatile anesthetic, sevoflurane has been proven to possess antiinflammatory and antioxidative properties. This study aims to investigate the protective effects of sevoflurane on inflammation and ventilator-induced lung injury during mechanical ventilation in healthy mice.
The adult healthy mice were divided into four groups, each consisting of ten subjects: mice in group Con-LVT and group Sev-LVT were ventilated with tidal volumes of 8 mL/kg for 4 hours, while those in group Con-HVT and group Sev-HVT were ventilated with tidal volumes of 16 mL/kg instead. Control mice (group Con-LVT and Con-HVT) were subjected to fresh air, while sevoflurane-treated mice (groups Sev- LVT and Sev-HVT) were subjected to air mixed with 1 vol% sevoflurane. After 4 hours of ventilation, the bronchoalveolar lavage (BAL) fluid was collected and analyzed for the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10. Lung homogenates were harvested to detect the expression of nuclear factor-kappa B (NF-κB) and heme oxygenase (HO)-1 mRNA by reverse transcription-polymerase chain reaction method. Lung damage was evaluated using the modified Ventilator-Induced Lung Injury histological scoring system.
Compared to group Con-LVT, the levels of TNF-α, IL-1β, IL-6, and IL-10 in BAL fluid, mRNA expressions of NF-κB and HO-1 in lung tissue, and lung injury scores were significantly increased in group Con-HVT; compared to group Con-HVT, group Sev-HVT BAL samples showed decreased levels of TNF-α, IL-1β, and IL-6; they also showed increased levels of IL-10, the downregulation of NF-κB mRNA, and HO-1 mRNA upregulation; the lung injury scores were significantly lower in group Sev-HVT than group Con-HVT.
Mechanical ventilation with high tidal volume might lead to lung injury, which could be significantly, but not completely, attenuated by sevoflurane inhalation by inhibiting the NF-κB-mediated proinflammatory cytokine generation and upregulating HO-1 expression.
PMCID: PMC3601644  PMID: 23515704
mechanical ventilation; sevoflurane; inflammation; lung injury
17.  Postconditioning of sevoflurane and propofol is associated with mitochondrial permeability transition pore*  
Background: Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postconditioning are unclear. Mitochondrial permeability transition pore (MPTP) opening is a major cause of ischemia-reperfusion injury. Here we investigated sevoflurane- and propofol-induced postconditioning and their relationship with MPTP. Methods: Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. During the first 15 min of reperfusion, hearts were treated with either control buffer (CTRL group) or buffer containing 20 µmol/L atractyloside (ATR group), 3% (v/v) sevoflurane (SPC group), 50 µmol/L propofol (PPC group), or the combination of atractyloside with respective anesthetics (SPC+ATR and PPC+ATR groups). Infarct size was determined by dividing the total necrotic area of the left ventricle by the total left ventricular slice area (percent necrotic area). Results: Hearts treated with sevoflurane or propofol showed significantly better recovery of coronary flow, end-diastolic pressures, left ventricular developed pressure and derivatives compared with controls. Sevoflurane resulted in more protective alteration of hemodynamics at most time point of reperfusion than propofol. These improvements were paralleled with the reduction of lactate dehydrogenase release and the decrease of infarct size (SPC vs CTRL: (17.48±2.70)% vs (48.47±6.03)%, P<0.05; PPC vs CTRL: (35.60±2.10)% vs (48.47±6.03)%, P<0.05). SPC group had less infarct size than PPC group (SPC vs PPC: (17.48±2.70)% vs (35.60±2.10)%, P<0.05). Atractyloside coadministration attenuated or completely blocked the cardioprotective effect of postconditioning of sevoflurane and propofol. Conclusion: Postconditioning of sevoflurane and propofol has cardioprotective effect against ischemia-reperfusion injury of heart, which is associated with inhibition of MPTP opening. Compared to propofol, sevoflurane provides superior protection of functional recovery and infarct size.
PMCID: PMC2225491  PMID: 18257131
Sevoflurane; Propofol; Postconditioning; Reperfusion injury; Mitochondrial permeability transition pore (MPTP)
18.  Intravenous palonosetron increases the incidence of QTc prolongation during sevoflurane general anesthesia for laparotomy 
Korean Journal of Anesthesiology  2013;65(5):397-402.
Palonosetron is a recently introduced 5-hydroxytryptamine-3 (5-HT3) receptor antagonist useful for postoperative nausea and vomiting prophylaxis. However, 5-HT3 receptor antagonists increase the corrected QT (QTc) interval in patients who undergo general anesthesia. This retrospective study was performed to evaluate whether palonosetron would induce a QTc prolongation in patients undergoing general anesthesia with sevoflurane.
We reviewed a database of 81 patients who underwent general anesthesia with sevoflurane. We divided the records into palonosetron (n = 41) and control (n = 40) groups according to the use of intraoperative palonosetron, and analyzed the electrocardiographic data before anesthesia and 30, 60, 90, and 120 min after skin incision. Changes in the QTc interval from baseline, mean blood pressure, heart rate, body temperature, and sevoflurane concentrations at each time point were compared between the two groups.
The QTc intervals at skin incision, and 30, 60, 90, and 120 min after the skin incision during general anesthesia were significantly longer than those at baseline in the two groups (P < 0.001). The changes in the QTc intervals were not different between the two groups (P = 0.41). However, six patients in the palonosetron group showed a QTc interval > 500 ms 30 min after skin incision, whereas no patient did in the control group (P = 0.01). No significant differences were observed between the two groups in mean blood pressure, body temperature, heart rate, or sevoflurane concentrations.
Palonosetron may induce QTc prolongation during the early general anesthesia period with sevoflurane.
PMCID: PMC3866334  PMID: 24363841
Cardiac arrhythmia; Electrocardiography; General anesthesia; Palonosetron; Patient safety; Sevoflurane
19.  Preconditioning of Mesenchymal Stem Cells by Sevoflurane to Improve Their Therapeutic Potential 
PLoS ONE  2014;9(3):e90667.
Bone marrow mesenchymal stem cells (MSCs) have been found to produce beneficial effects on ischemia-reperfusion injury. However, most of the MSCs died when transplanted into the ischemic tissue, which severely limit their therapeutic potential.
Using an in vitro model of hypoxia and serum deprivation (H/SD), we investigated the hypothesis that sevoflurane preconditioning could protect MSCs against H/SD-induced apoptosis and improve their migration, proliferation, and therapeutic potential. The H/SD of MSCs and neuron-like PC12 cells were incubated in a serum-free medium and an oxygen concentration below 0.1% for 24 h. Sevoflurane preconditioning was performed through a 2-h incubation of MSCs in an airtight chamber filled with 2 vol% sevoflurane. Apoptosis of MSCs or neuron-like PC12 cells was assessed using Annexin V-FITC/propidium iodide (PI). Furthermore, the mitochondrial membrane potential was assessed using lipophilic cationic probe. The proliferation rate was evaluated through cell cycle analysis. Finally, HIF-1α, HIF-2α, VEGF and p-Akt/Akt levels were measured by western blot.
Sevoflurane preconditioning minimized the MSCs apoptosis and loss of mitochondrial membrane potential. Furthermore, it increased the migration and expression of HIF-1α, HIF-2α, VEGF, and p-Akt/Akt, reduced by H/SD. In addition, neuron-like PC12 cells were more resistant to H/SD-induced apoptosis when they were co-cultured with sevoflurane preconditioning MSCs.
These findings suggest that sevoflurane preconditioning produces protective effects on survival and migration of MSCs against H/SD, as well as improving the therapeutic potential of MSCs. These beneficial effects might be mediated at least in part by upregulating HIF-1α, HIF-2α, VEGF, and p-Akt/Akt.
PMCID: PMC3944720  PMID: 24599264
20.  KATP channel blocker does not abolish the protective effect of NHE1 inhibition against ischaemia/reperfusion in aged myocardium 
Background and objective
Aging is associated with an increase in myocardial susceptibility to ischaemia/reperfusion (I/R) injury. Na+/H+ exchange (NHE) inhibition and anaesthetic preconditioning (APC) are shown to protect myocardium from I/R injury. We set out to investigate if NHE inhibition can induce protection against I/R injury and whether KATP channel inhibition can enhance this effect in aged rat myocardium.
Hearts from 24-month old rats were assigned to 4 groups: (1) Control group; (2) APC group perfused with 2.5% sevoflurane before ischemia; (3) HOE group perfused with (3-methylsulfonyl-4-piperidinobenzoyl) guanidine methanesulfonate (HOE-694) prior to ischaemia; (4) HOE+5HD group perfused with both HOE and 5-hydroxydecanoic acid before ischaemia. We measured intracellular Na+ and Ca++ to quantitate the severity of myocardial injury.
Both intracellular Na+ and Ca++ were significantly increased at the end of ischaemia and both were attenuated by NHE inhibition. Intracellular Na+ was 134±12 mEq/kg/dry weight in control group and 55±7 in HOE group (p<0.05). Intracellular Ca++ was 1764±142 nM in control group and 694±213 in HOE group (p<0.05). Infarct size was measured at 28±4% in control group vs. 17±2% in HOE group (p<0.05). High-energy phosphates and myocardial function were better preserved in HOE group compared to control (p<0.05). The beneficial effects of HOE on myocardial preservation was not blocked by 5HD nor were there any differences between APC and control groups.
NHE inhibition was effective in protecting myocardium from I/R injury in aged rats whereas APC was not. 5HD failed to block the protective effect of NHE inhibition.
PMCID: PMC2900462  PMID: 20216068
aged; anaesthetic preconditioning; NHE inhibition; myocardium; ischaemic/reperfusion injury
21.  Comparison of maintenance and emergence characteristics after desflurane or sevoflurane in outpatient anaesthesia 
Indian Journal of Anaesthesia  2011;55(1):36-42.
Both sevoflurane and desflurane have shorter emergence times compared to isoflurane based anaesthesia. Because of its pharmacological properties, desflurane appears to yield a rapid early and intermediate recovery compared with sevoflurane. The aim of this study was to assess the maintenance and emergence characteristics after anaesthesia with sevoflurane or desflurane. One hundred female patients scheduled to undergo daycare laparoscopic gynaecological surgery were enrolled for this prospective study. Patients were randomised into two groups to receive either desflurane [group I (D); n = 50] or sevoflurane [group II (S); n = 50] for maintenance of anaesthesia. The demographic data and the duration of procedure were comparable in both the groups. The early recovery time was shorter after maintenance of anaesthesia with desflurane compared with sevoflurane. However, this faster early recovery failed to lead to early readiness for home discharge. The intraoperative haemodynamic characteristics were comparable with both sevoflurane and desflurane. Both sevoflurane and desflurane provide a similar time to home readiness despite a faster early recovery with desflurane. The intraoperative haemodynamics are similar with both the agents.
PMCID: PMC3057243  PMID: 21431051
Desflurane; outpatient; recovery; sevoflurane
22.  Predictors of Disease Recurrence Post Living Donor Liver Transplantation in End Stage Chronic HCV Patients 
Disease Markers  2014;2014:202548.
HCV recurrence represents a universal phenomenon after liver transplantation. In this study Fifty HCV patients who underwent living donor liver transplantation were enrolled and factors that may accelerate HCV reinfection of the allograft such as donor's age and degree of liver steatosis, recipient's age, gender, BMI, MELD score, liver functions, HCV viral load, type of immunosuppressive drug, and genetic polymorphisms of IL28B, OAS, and IL1B were studied. The results of disease-free survival (DFS) rates showed inverse correlation with the recipient's postoperative levels of ALT, AST, ALP (P < 0.001, <0.001, and 0.006 resp.) as well as pre- and postoperative titers of HCV RNA (P < 0.003 and <0.001 resp.). Recipient's IL28B SNP was a significant factor in predicting postoperative DFS (P < 0.025). However, SNPs in OAS and IL1B genes had no apparent correlation with DFS. Cox proportional hazards model revealed that patients with elevated levels of ALT, preoperative viral titers, IL28B CT, and IL28B TT were 8.28, 4.22, 3.35, and 1.36 times, respectively, more likely to develop recurrence. In conclusion IL28B SNP, ALT level, and preoperative HCV titer besides proper choice of immunosuppressant are helpful for predicting posttransplant HCV recurrence and DFS.
PMCID: PMC3948502  PMID: 24695489
23.  The effect of warm liver ischaemia & reperfusion injury on circulating plasma lipid levels & lipolytic enzyme activity in rat & the impact of ischaemic preconditioning 
Background & objectives:
Ischaemia/reperfusion (I/R) associated with major liver surgery compromises liver function. Ischaemic preconditioning (IPC) may be effective in minimizing hepatic I/R injury. This study aimed to investigate the impact of liver ischaemic manipulations on lipid metabolism in rat during the process of liver recovery after liver surgery.
Sixty three male Wistar rats were assigned to three groups: the sham group, the I/R group which underwent warm ischaemia and reperfusion (I/R), and the IPC group. The animals were subdivided in 3 groups [1st, 3rdand 7th postoperative day (PO)]. Hepatic lipase (HL) and total lipase (TL) activity and the levels of aspartate and alanine transaminases (AST, ALT), triglycerides, HDL and cholesterol were measured in plasma.
There was no significant difference in the activity of HL and TL between the groups. Significant higher levels of HDL (P<0.0001) were observed in the IPC group when compared to the other groups on the 3rd PO day. Triglycerides (P<0.0001) and HDL (P=0.003) in the IPC group were higher than the sham group on the 7th PO day while HDL was also higher in the I/R group. Significantly higher cholesterol levels were found in the I/R and IPC groups on the 7th PO day, which were not observed in the sham group. There was a similar curve for triglycerides in the sham and IPC groups while there were significantly higher levels of triglycerides on day 7 for the I/R group. The levels of HDL in the IPC group were higher on the 3rd and 7th PO day, compared to day 1.
Interpretation & conclusion:
Warm ischaemia and I/R injury do not seem to affect lipolytic enzyme activity after the 1st PO day despite the effects on plasma lipids. IPC seems to prevent accumulation of triglycerides and cholesterol in plasma.
PMCID: PMC3461740  PMID: 22960895
Hepatic lipase; lipid metabolism; preconditioning; rat liver; warm ischaemia
24.  Vomiting after a pediatric adenotonsillectomy: comparison between propofol induced sevoflurane-nitrous oxide maintained anesthesia and TIVA with propofol-remifentanil 
Korean Journal of Anesthesiology  2010;59(3):185-189.
Anesthesia methods and drugs affect postoperative nausea and vomiting. Propofol is known to have antiemetic effects. We compared the incidence of postoperative vomiting (POV) in children undergoing an adenotonsillectomy; anesthesia in one group was induced with propofol and maintained with sevoflurane and nitrous oxide, and the other group received total intravenous anesthesia (TIVA) with propofol-remifentanil.
Ninety children, ASA physical status I, were assigned randomly to one of two groups. In the PSN group, anesthesia was maintained with 2-3 vol% sevoflurane and 50% nitrous oxide. In the PR group, anesthesia was maintained with 10 mg/kg/h propofol and 0.25 µg/kg/min remifentanil. In both groups, anesthesia was induced with 0.5 µg/kg remifentanil and 2 mg/kg propofol. The incidence of POV and the need for rescue antiemetics were assessed in the postanesthesia care unit at 6, 12, and 24 hours postoperatively.
The total incidence of POV was not significantly different between the groups; POV occurred in eight (17.7%) and three (6.7%) children in the PSN and PR groups, respectively. Postoperative frequency of retching in the recovery room was significantly higher in the PSN group, with four children (8.9%) in the PSN group compared to none (0%) in the PR group (P = 0.041). The frequency of POV 24 hrs after exiting the recovery room tended to be higher in the PSN group than the PR group, but no statistically significant difference was observed.
If the development of POV in the early anesthetic recovery phase of children undergoing adenotonsillectomy is adequately prevented, propofol-induced anesthesia maintained with sevoflurane-nitrous oxide is as safe as TIVA with propofol-remifentanil.
PMCID: PMC2946036  PMID: 20877703
Adenotonsillectomy; Pediatric; PONV; Sevoflurane; TIVA
25.  Effect of ondansetron in preventing postoperative nausea and vomiting under different conditions of general anesthesia: A preliminary, randomized, controlled study 
Two hundred and forty patients were randomly allocated into six groups: Group I, anesthesia was maintained with sevoflurane; Group II, anesthesia was maintained with sevoflurane and 8 mg of ondansetron; Group III, anesthesia was maintained with propofol; Group IV, anesthesia was maintained with propofol and 8 mg of ondansetron; Group V, anesthesia was maintained with sevoflurane and propofol; Group VI, anesthesia was maintained with sevoflurane combined with propofol and 8 mg of ondansetron.
We found that the incidence of vomiting was lower in group II (17.5%), group IV (7.5%), and group VI (10%) compared with group I (55%), group III (27.5%), and group V (30%), respectively (P < 0.05). The incidence of vomiting was also lower in group III (27.5%) and group V (30%) when compared with group I (55%) (P < 0.05). The incidence of nausea was 55% in group I, 42.5% in group II, 30% in group III, 27.5% in group IV, 30% in group V, and 30% in group VI. Groups III and V had a lower incidence of nausea than group I (P < 0.05).
We conclude that compared with sevoflurane anesthesia alone, anesthesia with either propofol alone or propofol combined with sevoflurane resulted in a reduced incidence of vomiting and nausea during the first 24 h after surgery. Administration of ondansetron effectively reduced the incidence of vomiting but not that of nausea for all three types of general anesthesia.
PMCID: PMC3633335  PMID: 23441598
general anesthesia; nausea; ondansetron; vomiting

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