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1.  SERUM CYTOKINE PROFILES ASSOCIATED WITH EARLY ALLOGRAFT DYSFUNCTION IN PATIENTS UNDERGOING LIVER TRANSPLANTATION 
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.
doi:10.1002/lt.22451
PMCID: PMC3266982  PMID: 22006860
immune monitoring; multiplex analysis; chemokines; immunobiology
2.  Effect of ischemic and pharmacological preconditioning of lower limb muscle tissue on tissue oxygenation measured by near-infrared spectroscopy – a pilot study 
BMC Anesthesiology  2014;14:54.
Background
Ischemic or volatile anesthetic preconditioning is defined as tissue protection from impending ischemic cell damage by repetitive short periods of tissue exposure to ischemia or volatile anesthetics. Objective of this study was to elucidate, if ischemic preconditioning and pharmacological preconditioning with sevoflurane have effects on muscle tissue oxygen saturation in patients undergoing surgical revascularization of the lower limb.
Methods
In this prospective randomized pilot study ischemic and pharmacological (sevoflurane) preconditioning was performed in 40 patients with lower limb arterial occlusive disease undergoing surgical revascularization. Sevoflurane preconditioning was performed in one group (N = 20) by repetitive application of sevoflurane for six minutes interspersed by six minutes of washout. Thereafter, ischemic preconditioning was performed in all patients (N = 40) by repetitive clamping of the femoral artery for six minutes interspersed by six minutes of reperfusion. The effect of both procedures on leg muscle tissue oxygen saturation (rSO2) was measured by near-infrared spectroscopy during both procedures and during surgery and reperfusion (INVOS® 5100C Oxymeter with Small Adult SomaSensor® SAFB-SM, Somanetics, Troy, Michigan, USA).
Results
Repetitive clamping and reperfusion of the femoral artery resulted in significant cyclic decrease and increase of muscle rSO2 (p < 0.0001). Pharmacological preconditioning with sevoflurane resulted in a faster and higher increase of rSO2 during postoperative reperfusion (Maximal 111% baseline ± 20 versus 103% baseline ± 14, p = 0.008) consistent with an additional effect of pharmacological preconditioning on leg perfusion.
Conclusions
Ischemic preconditioning of lower limb muscle tissue and pharmacological preconditioning with sevoflurane have an effect on tissue oxygenation in patients with lower limb occlusive arterial disease.
Trial registration
The trial has been registrated at http://www.ClinicalTrial.gov, Trial Number: NCT02038062 at 14 January 2014.
doi:10.1186/1471-2253-14-54
PMCID: PMC4134469  PMID: 25132803
Ischemic preconditioning; Sevoflurane; Surgical revascularization; Arterial occlusive disease
3.  Propofol or sevoflurane anaesthesia does not affect hepatic integrity as assessed by the M30 & M65 cell death markers & liver enzymes 
Background & objectives:
General anaesthetics may induce apoptosis. The pro-apoptotic/necrotic markers M30 (caspase-cleaved cytokeratin-18) and M65 (intact cytokeratin-18) have been used to identify early apoptosis in liver disease. The aim of this study was to detect the effect of propofol and sevoflurane anaesthesia on these markers and blood transaminase levels in female patients undergoing elective surgery.
Methods:
Sixty-seven women undergoing mastectomy or thyroidectomy under general anaesthesia were randomly allocated to the propofol or sevoflurane groups. Venous blood samples for measuring the apoptotic and necrotic markers M30 and M65 as well as for measuring the alanine aminotransferase (ALT) and the aspartate aminotransferase (AST) liver enzymes were collected before induction of anaesthesia, immediately after completion of surgery, and 24 and 48 h postoperatively.
Results.
The M30 values preoperatively and 0, 24 and 48 h postoperatively were 280±229, 300±244, 267±198 and 254±189 U/l in the propofol group and 237±95, 242±109, 231±94 and 234±127 U/l in the sevoflurane group, respectively. The M30 values did not differ within or between the groups. The M65 levels at the same time intervals were 470±262, 478±271, 456±339 and 485±273 in the propofol group and 427±226, 481±227, 389±158 and 404±144 U/l in the sevoflurane group, respectively. No significant changes were found in the M65 either within or between the propofol and the sevoflurane groups. The ALT and AST levels did not change at these time intervals.
Interpretation & conclusions:
Under the present study design propofol or sevoflurane anaesthesia did not induce apoptosis or affected the liver function as assessed by the M30, M65 markers and liver enzymes in patients undergoing mastectomy or thyroidectomy under general anaesthesia.
PMCID: PMC4311316  PMID: 25579144
Anaesthesia; apoptosis; liver; M30; M65; necrotic markers; propofol; sevoflurane
4.  The effect of preoperative suggestions on perioperative dreams and dream recalls after administration of different general anesthetic combinations: a randomized trial in maxillofacial surgery 
BMC Anesthesiology  2015;15(1):11.
Background
Images evoked immediately before the induction of anesthesia with the help of suggestions may influence dreaming during anesthesia.The aim of the study was to assess the incidence of evoked dreams and dream recalls by employing suggestions before induction of anesthesia while administering different general anesthetic combinations.
Methods
This is a single center, prospective randomized including 270 adult patients scheduled for maxillofacial surgical interventions. Patients were assigned to control, suggestion and dreamfilm groups according to the psychological method used. According to the anesthetic protocol there were also three subgroups: etomidate & sevoflurane, propofol & sevoflurane, propofol & propofol groups. Primary outcome measure was the incidence of postoperative dreams in the non-intervention group and in the three groups receiving different psychological interventions. Secondary endpoint was to test the effect of perioperative suggestions and dreamfilm-formation training on the occurrance of dreams and recallable dreams in different general anesthesiological techniques.
Results
Dream incidence rates measured in the control group did not differ significantly (etomidate & sevoflurane: 40%, propofol & sevoflurane: 26%, propofol & propofol: 39%). A significant increase could be observed in the incidence rate of dreams between the control and suggestion groups in the propofol & sevoflurane (26%-52%) group (p = 0.023). There was a significant difference in the incidence of dreams between the control and dreamfilm subgroup in the propofol & sevoflurane (26% vs. 57%), and in the propofol & propofol group (39% vs.70%) (p = 0.010, and p = 0.009, respectively). Similar to this, there was a significant difference in dream incidence between the dreamfilm and the suggestion subgroups (44% vs. 70%) in the propofol & propofol group (p = 0.019). Propofol as an induction agent contributed most to dream formation and recalls (χ2-test p value: 0.005). The content of images and dreams evoked using suggestions showed great agreement using all three anesthetic protocols.
Conclusion
The psychological method influenced dreaming during anesthesia. The increase of the incidence rate of dreams was dependent on the anesthetic agent used, especially the induction agent.
The study was registered in ClinicalTrials.gov. Identifier: NCT01839201.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2253-15-11) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2253-15-11
PMCID: PMC4328798
5.  Ischemic preconditioning induces autophagy and limits necrosis in human recipients of fatty liver grafts, decreasing the incidence of rejection episodes 
Cell Death & Disease  2011;2(1):e111-.
Whether ischemic preconditioning (IP) reduces ischemia/reperfusion (I/R) injury in human normal and fatty livers remains controversial. We compared two independent groups of liver donor transplants with versus without steatosis to evaluate IP consequences. Liver donors with (n=22) or without (n=28) steatosis either did or did not undergo IP before graft retrieval. Clinical data from the recipients, as well as histological and immunohistological characteristics of post-reperfusion biopsies were analyzed. Incidence of post-reperfusion necrosis was increased (10/10 versus 9/14, respectively; P<0.05) and the clinical outcome of recipients was worse for non-IP steatotic liver grafts compared with non-IP non-steatotic grafts. IP significantly lowered the transaminase values only in patients receiving a non-steatotic liver. An increased expression of beclin-1 and LC3, two pro-autophagic proteins, tended to decrease the incidence of necrosis (P=0.067) in IP steatotic livers compared with non-IP steatotic group. IP decreased the incidence of acute and chronic rejection episodes in steatotic livers (2/12 versus 6/10; P=0.07 and 2/12 versus 7/10; P<0.05, respectively), but not in non-steatotic livers. Thus, IP may induce autophagy in human steatotic liver grafts and reduce rejection in their recipients.
doi:10.1038/cddis.2010.89
PMCID: PMC3077285  PMID: 21368883
steatosis; liver transplantation; ischemia/reperfusion; ischemic preconditioning; autophagy; liver
6.  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.
Conclusions
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
ClinicalTrials.gov NCT01199913
doi:10.1186/2045-9912-4-6
PMCID: PMC3976084  PMID: 24666542
General anesthesia; Postoperative cognitive decline; Geriatric patient
7.  Effect of sevoflurane on grafted kidney function in renal transplantation 
Korean Journal of Anesthesiology  2012;62(6):529-535.
Background
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.
Methods
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.
Results
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.
Conclusions
Compared to desflurane, sevoflurane had no adverse effects on grafted renal function or on the short-term outcome of renal transplantation.
doi:10.4097/kjae.2012.62.6.529
PMCID: PMC3384790  PMID: 22778888
Creatinine; Glomerular filtration rate; Kidney transplantation; Sevoflurane
8.  Donor Graft Steatosis Influences Immunity to Hepatitis C Virus and Allograft Outcome After Liver Transplantation 
Transplantation  2011;92(11):1259-1268.
Background
Hepatitis C (HCV) recurrence following orthotopic liver transplantation (OLT) is universal, often with accelerated allograft fibrosis. Donor liver steatosis is frequently encountered and often associated with poor early post-operative outcome. The study’s aim was to test the hypothesis that allograft steatosis alters immune responses to HCV and self-antigens promoting allograft fibrosis.
Methods
Forty-eight HCV OLT recipients (OLTr) were enrolled and classified based on amount of allograft macrovesicular steatosis at time of OLT. Group 1-No Steatosis (0–5% steatosis, n=21), Group 2 – Mild (5–35% - n=16), Group 3 – moderate (>35%, n=11). Cells secreting IL-17, IL-10, IFN-γ in response to HCV antigens were enumerated by ELISpot. Serum cytokines were measured by Luminex, antibodies (Abs) to Collagen (Col) I, II, III, IV, V by ELISA.
Results
OLTr of moderate steatotic grafts had the highest incidence of advanced fibrosis in protocol one-year post-OLT biopsy (10.8% vs. 15.8% vs. 36.6%, r = 0.157, p<0.05). OLTr from Groups 2 and 3 had increased HCV specific IL-17 (p<0.05) and IL-10 (p<0.05) with reduced IFN-γ (p<0.05) secreting cells when compared to group 1. This was associated with increase in serum IL-17, IL-10, IL-1β, IL-6, IL-5 and decreased IFN-γ. In addition, there was development of Abs to Col I, II, III and V in OLTr with increased steatosis (p<0.05).
Conclusion
The results demonstrate that allograft steatosis influences post-OLT HCV specific immune responses leading to a IL-17 T-helper response and activation of humoral immune responses to liver associated self antigens which may contribute to allograft fibrosis and poor outcome.
doi:10.1097/TP.0b013e318235a1ab
PMCID: PMC3223266  PMID: 22011763
Allograft Steatosis; Hepatitis C; Recurrence; Fibrosis; Liver Transplantation
9.  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.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.4097/kjae.2013.64.2.112
PMCID: PMC3581778  PMID: 23459368
Alanine aminotransferase; Aspartate aminotransferase; Blood Urea Nitrogen (BUN); Creatinine; Inhalation anesthesia; Total intravenous anesthesia
10.  Myocardial blood flow under general anaesthesia with sevoflurane in type 2 diabetic patients: a pilot study 
Background
In type 2 diabetic patients, cardiac events in the perioperative period may be associated with diminished myocardial vasomotor function and endothelial dysfunction. The influence of sevoflurane anaesthesia on myocardial endothelial dysfunction in type 2 diabetic mellitus is investigated in this pilot study.
Methods
Six males with type 2 diabetes mellitus and eight healthy controls were included. Using myocardial contrast echocardiography, myocardial blood flow (MBF) was measured at rest, during adenosine-induced hyperaemia (endothelium-independent vasodilation) and after sympathetic stimulation by the cold pressor test (endothelium-dependent vasodilation). Measurements were performed before and after induction of sevoflurane anaesthesia.
Results
Sevoflurane anaesthesia decreased resting MBF in diabetics but not in controls (P = 0.03), while baseline MBF did not differ between diabetics and controls. Without anaesthesia, adenosine-induced hyperaemia increased MBF in both groups compared to resting values. Adenosine combined with sevoflurane resulted in a lower hyperaemic MBF in both groups compared to no anaesthesia. Differences in MBF in response to adenosine before and after sevoflurane administration were larger in diabetic patients, however not statistically significant in this pilot group (P = 0.08). Myocardial blood flow parameters after the cold pressor test were not different between groups.
Conclusion
These pilot data in type 2 diabetic patients show that sevoflurane anaesthesia decreases resting myocardial blood flow compared to healthy controls. Further, we observed a trend towards a lower endothelium-independent vasodilation capacity in diabetic patients under sevoflurane anaesthesia. Endothelium-dependent vasodilation was not affected by sevoflurane in diabetic patients. These data provide preliminary insight into myocardial responses in type 2 diabetic patients under general anaesthesia.
Trial registration
http://www.clinicialtrials.gov, NCT00866801
doi:10.1186/1475-2840-13-62
PMCID: PMC3994329  PMID: 24656118
Type 2 diabetes mellitus; Myocardial blood flow; Anaesthesia; Hyperaemia
11.  Influence of the Sevoflurane Concentration on the Occurrence of Epileptiform EEG Patterns 
PLoS ONE  2014;9(2):e89191.
Objectives and Aim
This study was performed to analyse the effects of different sevoflurane concentrations on the incidence of epileptiform EEG activity during induction of anaesthesia in children in the clinical routine.
Background
It was suggested in the literature to use sevoflurane concentrations lower than 8% to avoid epileptiform activity during induction of anaesthesia in children.
Methods
100 children (age: 4.6±3.0 years, ASA I–III, premedication with midazolam) were anaesthetized with 8% sevoflurane for 3 min or 6% sevoflurane for 5 min in 100% O2 via face mask followed by 4% sevoflurane until propofol and remifentanil were given for intubation. EEGs were recorded continuously and were analysed visually with regard to epileptiform EEG patterns.
Results
From start of sevoflurane until propofol/remifentanil administration, 38 patients (76%) with 8% sevoflurane had epileptiform EEG patterns compared to 26 patients (52%) with 6% (p = 0.0106). Epileptiform potentials tended to appear later in the course of the induction with 6% than with 8%. Up to an endtidal concentration of 6% sevoflurane, the number of children with epileptiform potentials was similar in both groups (p = 0.3708). The cumulative number of children with epileptiform activity increased with increasing endtidal sevoflurane concentrations. The time from start of sevoflurane until loss of consciousness was similar in patients with 8% and 6% sevoflurane (42.2±17.5 s vs. 44.9 s ±14.0 s; p = 0.4073). An EEG stage of deep anaesthesia with continuous delta waves <2.0 Hz appeared significantly earlier in the 8% than in the 6% group (64.0±22.2 s vs. 77.9±20.0 s, p = 0.0022).
Conclusion
The own analysis and data from the literature show that lower endtidal concentrations of sevoflurane and shorter administration times can be used to reduce epileptiform activity during induction of sevoflurane anaesthesia in children.
doi:10.1371/journal.pone.0089191
PMCID: PMC3935848  PMID: 24586585
12.  The Effects of Intraoperative Adenosine Infusion on Acute Opioid Tolerance and Opioid Induced Hyperalgesia Induced by Remifentanil in Adult Patients Undergoing Tonsillectomy 
The Korean Journal of Pain  2011;24(1):7-12.
Background
Adenosine has been shown to have a wide spectrum of unique pain-relieving effects in various clinical situations. The aim of this study was to investigate the effects of intraoperative adenosine infusion on acute opioid tolerance and opioid induced hyperalgesia induced by remifentanil in adult patients undergoing tonsillectomy.
Methods
For this study, ninety patients were randomly allocated into groups that receive either adenosine (adenosine group) or saline (remifentnail group) intravenously under remifentanil based anesthesia and saline (sevoflurane group) under sevoflurane anesthesia. The patients in adenosine group received adenosine at dose of 80 µg/kg/min, and those in remifentnail group and sevoflurane group received an equal volume of saline 10 minutes after the induction of anesthesia until the end of surgery. Intraoperative evaluation included time weighted mean remifentanil dose, and postoperative evaluations included degree of pain severity at 1, 6, 12, and 24 hours, time to first postoperative requirement, and analgesic dose required during 24 hours after operation.
Results
Time weighted mean remifentanil dose during intraoperative period in adenosine group was significantly lower than that of remifentnail group (P = 0.00). The first postoperative analgesic were required earlier in remifentanil group than sevoflurane group or adenosine group (P = 0.00). Pethidine requirement during 24 hours in sevoflurane group and adenosine group was significantly lower than that of remifentnail group (P = 0.00). The visual analog scale scores for pain in sevoflurane group and adenosine group were significantly lower than those of remifentnail group for 12 hours after operation (P = 0.00). Incidence of hypotension (P = 0.024) and number of ephedrine administered (P = 0.011) in adenosine group were significantly higher than those of sevoflurane group.
Conclusions
The above results suggest that intraoperative adenosine infusion prevent acute opioid tolerance and opioid induced hyperalgesia induced by remifentanil.
doi:10.3344/kjp.2011.24.1.7
PMCID: PMC3049980  PMID: 21390173
adenosine; analgesic requirement; opioid induced hyperalgesia; remifentanil
13.  Comparison of emergence agitation between sevoflurane/nitrous oxide administration and sevoflurane administration alone in children undergoing adenotonsillectomy with preemptive ketorolac 
Background
Sevoflurane anesthesia commonly causes emergence agitation (EA) in children. One previous study has reported that the use of nitrous oxide (N2O) during the washout of sevoflurane may reduce EA by decreasing the residual sevoflurane concentration, while many animal studies suggest that N2O poses a potential risk to children. The present study was designed to compare EA in children assigned to receive sevoflurane with N2O (group N) or sevoflurane alone (group S).
Methods
We enrolled 80 children aged 3-10 years. Anesthesia was induced with 5 mg/kg thiopental sodium, 0.6 mg/kg rocuronium and 0.5 mg/kg ketorolac, and was maintained with 50% N2O and sevoflurane in group N or with sevoflurane alone in group S. The sevoflurane concentration was adjusted with a bispectral index (BIS) of 40-60. After completion of the surgery, N2O and sevoflurane were simultaneously discontinued and replaced with oxygen (O2) at 6 L/min. End-tidal sevoflurane concentration (Et Sevo) (%), BIS at the end of surgery, Et Sevo at recovery of self-respiration and emergence profiles were recorded. EA occurrence, pain score and rescue fentanyl consumption were assessed in the postanesthesia care unit.
Results
Et Sevo was significantly lower in group N (1.9%) than in group S (2.3%) at the end of surgery. However, there were no differences in Et Sevo at recovery of self-respiration, emergence times, the incidence of EA, pain score or dose of rescue fentanyl between the groups.
Conclusions
In children undergoing adenotonsillectomy with preemptive ketorolac, anesthetic maintenance using sevoflurane alone does not affect the incidence of EA or emergence profiles compared to anesthetic maintenance using sevoflurane with N2O.
doi:10.4097/kjae.2014.66.1.34
PMCID: PMC3926999  PMID: 24567811
Emergence agitation; Nitrous oxide; Sevoflurane; Tonsillectomy and adenoidectomy
14.  Comparison of recovery profile for propofol and sevoflurane anesthesia in cases of open cholecystectomy 
Objective:
Sevoflurane and propofol are considered to be the agents of choice in surgeries of short duration due to their better recovery profile and few post-operative complications. This study was designed to compare the early recovery profile of sevoflurane and propofol anesthesia in patients undergoing open cholecystectomy.
Materials and Methods:
A total of 60 patients of either sex with American Society of Anesthesiologists grade 1 and 2 scheduled for elective cholecystectomy were prospectively randomized into two groups. Group S (30 patients) were maintained with sevoflurane anesthesia (1-2%), while in Group P (30 patients) were maintained with propofol infusion (75-125 μg/kg/min) in both the groups the anesthetic concentration/dose was so adjusted to keep hemodynamic parameter (mean arterial pressure and heart rate) within 15% of their respective baselines values.
Results:
It was observed that there was no significant difference (P > 0.05) between there early recovery profile that includes spontaneous eye opening (7.5 ± 1.6 min for sevoflurane group and 6.9 ± 1.7 min for propofol group), following simple verbal command (9.2 ± 2.2 min for sevoflurane group and 8.9 ± 1.9 min for propofol group) and extubation time (10.7 ± 2.3 min for sevoflurane group and 10.3 ± 2.0 min for propofol group) but there was a significant difference (P < 0.05) in incidence of post-operative nausea and vomiting (PONV) in both groups.
Conclusion:
Propofol is as good as sevoflurane for maintenance of anesthesia in surgeries like open cholecystectomy with an added advantage of lower incidence of PONV owing to its intrinsic antiemetic properties.
doi:10.4103/0259-1162.123259
PMCID: PMC4173547
Cholecystectomy; propofol; recovery profile; sevoflurane
15.  Cardioprotective effect of sevoflurane in patients with coronary artery disease undergoing vascular surgery 
Saudi Journal of Anaesthesia  2012;6(2):125-130.
Objectives:
The present study was conducted to evaluate the cardioprotective effect of sevoflurane compared with propofol in patients with coronary artery disease (CAD) undergoing peripheral vascular surgery; and to address the question whether a volatile anesthetic might improve cardiac outcome in these patients.
Methods:
One hundred twenty-six patients scheduled for elective peripheral vascular surgery were prospectively randomized to receive either sevoflurane inhalation anesthesia or total intravenous anesthesia. ST-segment monitoring was performed continuously during intra- and post-operative 48 h periods. The number of ischemic events and the cumulative duration of ischemia in each patient were recorded. Blood was sampled in all patients for the determination of cTnI. Samples were obtained before the induction of anesthesia, on admission to the ICU, and at 6, 12, 24, and 48 h after admission to the intensive care unit (ICU). Patients were followed-up during their hospital stay for any adverse cardiac events.
Results:
The incidence of ischemia were comparable among the groups [16 (25%) patients in sevoflurane group vs 24 (39%) patients in propofol group; P=0.126]. Duration, cumulative duration, and magnitude of ST-segment depression of ischemic events in each patient were significantly less in sevoflurane group (P=0.008, 0.048, 0.038, respectively). cTnI levels of the overall population were significantly less in sevoflurane group vs propofol group (P values <0.0001) from 6 h postoperative and onward. Meanwhile, cTnI levels at 6, 12, 24, and 48 h after admission to the ICU in patients who presented with ischemic electrocardiographic (ECG) changes were significantly lower in sevoflurane group than in the propofol group (P<0.0001, <0.0001, <0.0001, 0.0003). None of the patients presented with unstable angina, myocardial infarction, congestive heart failure, or serious arrhythmia either during ICU or hospital stay.
Conclusion:
Patients with CAD receiving sevoflurane for peripheral vascular surgery had significantly lower release of cardiac troponin I at 6 h postoperatively and lasting for 48 h than patients receiving propofol for the same procedure with significant decrease in duration, cumulative duration of ischemic events, and degree of ST depression in each patient.
doi:10.4103/1658-354X.97024
PMCID: PMC3385253  PMID: 22754437
Coronary artery disease; cardioprotective; sevoflurane; vascular surgery
16.  Oxygen persufflation as adjunct in liver preservation (OPAL): Study protocol for a randomized controlled trial 
Trials  2011;12:234.
Background
Early graft dysfunction due to preservation/reperfusion injury represents a dramatic event after liver transplantation. Enhancement of donor organ criteria, in order to cope with the ever increasing donor shortage, further increases graft susceptibility to ischemic alterations.
Major parts of post-preservation injury, however, occur at the time of warm reperfusion but not during ischemic storage; successful reperfusion of ischemic tissue in turn depends on an adequate redox and intracellular signal homeostasis. The latter has been shown experimentally to be favorably influenced by oxygen persufflation within short time spans. Thus viability of marginally preserved liver grafts could still be augmented by transient hypothermic reconditioning even after normal procurement and static cold storage. The present study is aimed to confirm the conceptual expectations, that hypothermic reconditioning by gaseous oxygen persufflation is a useful method to suppress injurious cellular activation cascades and to improve post-ischemic recovery of marginally preserved liver grafts.
Methods/Design
OPAL is a prospective single center randomized proof of concept study, including two parallel groups in a total of 116 liver transplant patients. The effect of an in hospital treatment of the isolated liver graft by 2 hours of oxygen persufflation immediately prior to transplantation will be assesses as compared to standard procedure (cold storage without further intervention). The primary endpoint is the peak transaminase serum level (AST) during the first three days after transplantation as a surrogate readout for parenchymal liver injury. Other outcomes comprise patient and graft survival, time of intensive care requirement, hepatic tissue perfusion 1h after revascularisation, early onset of graft dysfunction based on coagulation parameters, as well as the use of a refined scoring-system for initial graft function based on a multi-parameter (AST, ALT, Quick and bilirubin) score. Furthermore, the effect of OPAL on molecular pathways of autophagy and inflammatory cell activation will be evaluated. Final analysis will be based on all participants as randomized (intention to treat).
Trial Registration
Current Controlled Trials ISRCTN00167887
doi:10.1186/1745-6215-12-234
PMCID: PMC3215181  PMID: 22035223
17.  Effects of repeat exposure to inhalation anesthetics on liver and renal function 
Background:
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.
Results:
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.
Conclusions:
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.
doi:10.4103/0970-9185.105809
PMCID: PMC3590549  PMID: 23493664
General anesthesia; isoflurane; kidney; liver; propofol; sevoflurane
18.  Comparison of recovery profiles of propofol and sevoflurane anesthesia with bispectral index monitoring in percutaneous nephrolithotomy 
Korean Journal of Anesthesiology  2013;64(3):223-228.
Background
The aim of the study was to evaluate the comparative effects of propofol infusion versus sevoflurane for maintenance of anesthesia with respect to hemodynamics, recovery characteristics, nausea and vomiting in patients undergoing percutaneous nephrolithotomy.
Methods
Forty American Society of Anesthesiologists physical status I-II patients, aged between 22 and 65 years were randomly divided to receive either intravenous anesthesia with propofol (group P) or sevoflurane (group S). Cardiovascular variables, peripheral oxygen saturation (SpO2), end-tidal carbon dioxide (ETCO2), bispectral index (BIS) and train-of-four (TOF) values were recorded at intervals throughout the procedure. Time to spontaneous respiration, eye opening, extubation, obey commands, hand squeezing, Aldrete Score > 9 and the incidence of postoperative nausea and vomiting were recorded.
Results
Early recovery times [spontaneous respiration (P = 0.002), eye opening (P = 0.006), extubation (P = 0.013), obey commands (P < 0.05), hand squeezing (P = 0.005)] were significantly longer in group P. The incidence of vomiting was significantly higher in group S (P < 0.05). Hemodynamic parameters, levels of SpO2, ETCO2, and BIS and TOF values were not significantly different between the groups (P > 0.05).
Conclusions
The present study which adjusted sevoflurane concentration and propofol infusion rate according to BIS values revealed that maintenance of anesthesia with sevoflurane is associated with faster recovery than anesthesia with propofol. Propofol resulted in a significantly lower incidence of postoperative nausea and vomiting. Hemodynamic parameters and levels of SpO2 and ETCO2 were comparable between the groups during percutaneous nephrolithotomy.
doi:10.4097/kjae.2013.64.3.223
PMCID: PMC3611071  PMID: 23560187
Percutaneous nephrolithotomy; Propofol; Sevoflurane
19.  Sevoflurane preconditioning ameliorates neuronal deficits by inhibiting microglial MMP-9 expression after spinal cord ischemia/reperfusion in rats 
Molecular Brain  2014;7(1):69.
Background
Microglia are the primary immune cells of the spinal cord that are activated in response to ischemia/reperfusion (IR) injury and release various neurotrophic and/or neurotoxic factors to determine neuronal survival. Among them, matrix metalloproteinase-9 (MMP-9), which cleaves various components of the extracellular matrix in the basal lamina and functions as part of the blood spinal cord barrier (BSCB), is considered important for regulating inflammatory responses and microenvironmental homeostasis of the BSCB in the pathology of ischemia. Sevoflurane has been reported to protect against neuronal apoptosis during cerebral IR. However, the effects of sevoflurane preconditioning on spinal cord IR injury remain unclear. In this study, we investigated the role of sevoflurane on potential genetic roles of microglial MMP-9 in tight junction protein breakdown, opening of the BSCB, and subsequent recruitment of microglia to apoptotic spinal cord neurons.
Results
The results showed significant upregulation of MMP-9 in rats with IR-induced inflammation of the BSCB compared to that of the sham group, manifested as dysfunctional BSCB with increased Evans blue extravasation and reduced expression of occludin protein. Increased MMP-9 expression was also observed to facilitate invasion and migration of activated microglia, imaging as high Iba-1 expression, clustered to neurons in the injured spinal cord, as shown by double immunofluorescence, and increased proinflammatory chemokine production (CXCL10, CCL2). Further, sevoflurane preconditioning markedly improved motor function by ameliorating neuronal apoptosis, as shown by reduced TUNEL-positive cell counts and expression of cleaved caspase-3. These protective effects were probably responsible for downregulation of MMP-9 and maintenance of normal expression of occludin protein indicating BSCB integrity from inflammatory damage, which was confirmed by decreased protein levels of Iba-1 and MMP-9, as well as reduced production of proinflammatory chemokines (CXCL10, CCL2) and proinflammatory cytokines (IL-1β). Intrathecal injection of specific siRNAs targeting MMP-9 had similar protective effects to those of sevoflurane preconditioning.
Conclusions
Preconditioning with 2.4% sevoflurane attenuated spinal cord IR injury by inhibiting recruitment of microglia and secretion of MMP-9; thus inhibiting downstream effects on inflammatory damage to BSCB integrity and neuronal apoptosis.
Electronic supplementary material
The online version of this article (doi:10.1186/s13041-014-0069-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s13041-014-0069-7
PMCID: PMC4161899  PMID: 25186151
Apoptosis; Blood spinal cord barrier; Matrix metalloproteinase; Microglia; Neuron; Spinal cord ischemia/reperfusion injury
20.  Comparison between low flow sevoflurane anesthesia and total intravenous anesthesia during intermediate-duration surgery: effects on renal and hepatic toxicity 
Hippokratia  2011;15(1):69-74.
Background: Renal and hepatic dysfunction or injury might be involved by ether based anesthetic and intravenous anesthetic drug or surgical stress. The purpose of this study is to compare the effect of moderate duration low-flow sevoflurane versus total intravenous anesthesia on renal and hepatic functions.
Patients and Methods: Eighty (80) patients between the ages of 25-70 scheduled for elective lumbar disc herniotomy, with an expected operation time of 120-240 min, were enrolled in the study. Anesthesia was induced using remifentanil, propofol and atracurium. Patients were randomly divided into two groups. After intubation, Group S (n=40) received sevoflurane and Group T (n=40) received total intravenous anesthesia with propofol in oxygen and air with a fresh gas flow of 5 L min?1. Ten minutes after induction the fresh gas flow was decreased to 1L min?1 in both groups. Serum BUN, creatinine, ALT, AST, LDH and 24 hours excretion of glucose, protein, and creatinine in urine were measured preoperatively and the first three postoperative days.
Results: Serum BUN at 48 hours, creatinine at 24, 48. hours, and urine glucose at 24, and 48 hours were significantly higher from the preoperative values in Group S (p<0.05). However, serum BUN and creatinin, urine glucose were within the normal range. There were no significant differences in the renal and hepatic function tests between the groups.
Conclusions: These results show that the renal and hepatic effect of moderate duration low-flow sevoflurane and total intravenous anesthesia is similar.
PMCID: PMC3093149  PMID: 21607040
anesthesia; general; sevoflurane; low; flow anesthesia; analgesics; opioid; remifentanil; propofol; kidney
21.  Postoperative nausea and vomiting after endoscopic thyroidectomy: total intravenous vs. balanced anesthesia 
Korean Journal of Anesthesiology  2011;60(6):416-421.
Background
Endoscopic thyroidectomy was recently introduced and has been rapidly accepted by surgeons and patients. The present study was conducted to estimate and compare the incidences of postoperative nausea and vomiting (PONV) after endoscopic thyroidectomy using two different anesthetic methods: sevoflurane based balanced anesthesia; total intravenous anesthesia (TIVA).
Methods
Ninety nine female patients that were scheduled to undergo elective endoscopic thyroidectomy under general anesthesia were enrolled. These patients were randomly allocated to receive sevoflurane based balanced anesthesia (BA group) or propofol-remifentanil anesthesia (TIVA group). PONV was evaluated using a 4-point Likert scale, and pain using a visual analogue scale (VAS; range 0 to 100) for 0-2, 2-6, and 6-24 hours postoperatively. At 24 hours postoperatively, overall patient satisfaction regarding PONV and pain were recorded.
Results
The incidence of PONV was 14.6% in the TIVA group and 51.3% in the BA group. The incidence of nausea at 0-2 and 2-6 hours postoperatively was lower in the TIVA group than in the BA group (4.2% vs. 35.9%, 6.3% vs. 23.1%, respectively), but no between-group difference was observed at 6-24 hours postoperatively (8.3% vs. 5.1%). Antiemetic usage at 0-2 and 2-6 hours was lower in the TIVA than the BA group (4.2% vs. 38.5%, 6.3% vs. 23.1%), but no between-group difference was observed for 6-24 hours (6.3% vs. 7.7%). There were no differences in pain or in patient satisfaction.
Conclusions
After endoscopic thyroidectomy, total intravenous anesthesia with propofol-remifentanil is associated with less PONV during the early postoperative period (0-6 hours) than sevoflurane based balanced anesthesia.
doi:10.4097/kjae.2011.60.6.416
PMCID: PMC3121088  PMID: 21738844
Endoscopic surgery; PONV; Thyroidectomy
22.  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.
doi:10.1631/jzus.B0900390
PMCID: PMC2852543  PMID: 20349523
Inhalation anesthetics; Sevoflurane; Postconditioning; Preconditioning; Ischemia-reperfusion injury; Myocardial stunning
23.  Risk factors for early postoperative cognitive dysfunction after non-coronary bypass surgery in Chinese population 
Background
The present study was performed to investigate the incidence of early postoperative cognitive dysfunction (POCD) after non-coronary bypass surgery and the potential risk factors in Chinese population.
Methods
We performed a prospective study in a teaching tertiary hospital from May 2012 to August 2012. One hundred and seventy-six adult patients undergoing non-coronary bypass surgery were recruited. Mini-Mental State Examination (MMSE) score was evaluated before and 3 to 5 days after surgery. Patients with a MMSE score reduction of 2 was diagnosed with POCD.
Results
The general incidence of POCD was 33.0%, with no significant difference between the types of surgeries. In the univariate analysis, POCD associated factors included age, duration of surgery, anesthesia, cardiopulmonary bypass (CPB), cross-clamp and rewarming, and sevoflurane concentration. However, only age, cross-clamp duration and sevoflurane concentration were demonstrated to be independent risk factors for POCD.
Conclusion
Incidence of early POCD after non-coronary bypass surgery was relatively high in Chinese population. Advanced age, longer aortic cross-clamp duration and lower sevoflurane concentration was associated with a higher incidence of POCD.
doi:10.1186/1749-8090-8-204
PMCID: PMC3818927  PMID: 24175992
Postoperative cognitive dysfunction; Cardiovascular surgery; Risk factor; Sevoflurane
24.  Comparison of isoflurane and sevoflurane in anaesthesia for day care surgeries using classical laryngeal mask airway 
Indian Journal of Anaesthesia  2011;55(4):364-369.
Background:
In the present study, we compared isoflurane with sevoflurane in day care surgeries in order to determine the suitability of each agent for anaesthesia with Classical laryngeal mask airway (LMA).
Aims:
The aim of this study has been to compare isoflurane and sevoflurane as maintenance anaesthetic agents in day care surgeries with respect to intraoperative haemodynamics, recovery profile, time of first postoperative analgesia and pain score, adverse effects when used with classical LMA.
Settings and Design:
This open - level, prospective randomized study was carried out on 60 patients who were admitted on a day care basis for elective short surgical procedures.
Methods:
The patients were randomly assigned to one of the two study groups of 30 patients each. First group was maintained on isoflurane and second on sevoflurane as inhalational agent.
Statistical Analysis:
The observations obtained in both the groups were recorded and tabulated. Statistical analysis was carried out using the Student t test, Chi-square test, Mann-Whitney test.
Results:
Emergence from Sevoflurane was significantly quicker as compared to isoflurane. Sevoflurane group also showed earlier discharge time from the post anaesthesia care unit (PACU)-1 as compared to isoflurane group, but discharge time was same from the PACU-1. Isoflurane has more incidences of mild airway hyper reactivity when compared to sevoflurane.
Conclusions:
It can be concluded that both isoflurane and sevoflurane are suitable for day care anaesthesia. Sevoflurane has little advantages of less airway hyper reactivity and quicker emergence and discharge from PACU-1.
doi:10.4103/0019-5049.84857
PMCID: PMC3190510  PMID: 22013252
Anaesthesia; classical laryngeal mask airway; day care surgery; isoflurane; sevoflurane
25.  Early cognitive function, recovery and well-being after sevoflurane and xenon anaesthesia in the elderly: a double-blinded randomized controlled trial 
Background
The postoperative cognitive function is impaired in elderly patients after general anaesthesia. The fast recovery after xenon anaesthesia was hypothesized to be advantageous in this scenario. We compared early postoperative cognitive function after xenon and sevoflurane anaesthesia in this study.
Methods
The study was approved by the local ethics committee and written informed consent was obtained from each patient. Patients aged 65-75 years (ASA I-III) scheduled for elective surgery (duration 60-180 min) were enrolled. Investigators performing cognitive testing and patients were blinded towards allocation to either xenon or sevoflurane anaesthesia. Baseline assessment of cognitive function was carried out 12-24 h before the operation. The results were compared to follow-up tests 6-12 and 66-72 h after surgery. Primary outcome parameter was the subtest "Alertness" of the computerized Test of Attentional Performance (TAP). Secondary outcome parameters included further subtests of the TAP, several Paper-Pencil-Tests, emergence times from anaesthesia, modified Aldrete scores and patients' well-being.
Results
40 patients were randomized and equally allocated to both groups. No significant differences were found in the TAP or the Paper-Pencil-Tests at 6-12 and 66-72 h after the operation. All emergence times were faster after xenon anaesthesia. The modified Aldrete scores were significantly higher during the first hour in the xenon group. No difference in well-being could be detected between both groups.
Conclusions
The results show no difference in the incidence of postoperative cognitive dysfunction (POCD) after xenon or sevoflurane anaesthesia. Emergence from general anaesthesia was faster in the xenon group.
doi:10.1186/2045-9912-1-9
PMCID: PMC3231879  PMID: 22146537

Results 1-25 (750006)