Sevoflurane is one of the most commonly used inhaled anesthetics in obstetric and pediatric general anesthesia.According to related literature,this article reviews major possible mechanisms including myelin formation damage,nerve inflammation,cell apoptosis,oxidative stress,inhibition of histone acetylation,synapsis and receptor changes of sevoflurane-induced neurotoxicity in animal experiments.Furthermore,we summarize the neuroprotection effects and functioning mechanisms of anti-anemia medicine,plant-based drugs,alpha 2 adrenoceptor agonists and others,aiming to provide a basis for the brain protection of fetuses and infants during the perioperative period.
Anesthetics, Inhalation/adverse effects* ; Animals ; Apoptosis ; Brain ; Child ; Female ; Humans ; Methyl Ethers ; Neuroprotective Agents/therapeutic use* ; Oxidative Stress ; Pregnancy ; Sevoflurane

Pulmonary dysfunction caused by ischemia-reperfusion injury is the leading cause of mortality in lung transplantation. We aimed to investigate the effects of sevoflurane pretreatment on lung permeability, tight junction protein occludin and zona occludens 1 (ZO-1) expression, and translocation of protein kinase C (PKC)-alpha after ischemia-reperfusion. A lung ischemia-reperfusion injury model was established in 96 male Wistar rats following the modified Eppinger method. The rats were divided into four groups with 24 rats in each group: a control (group C), an ischemia-reperfusion group (IR group), a sevoflurane control group (sev-C group), and a sevoflurane ischemia-reperfusion group (sev-IR group). There were three time points in each group: ischemic occlusion for 45 min, reperfusion for 60 min and reperfusion for 120 min; and there were six rats per time point. For the 120-min reperfusion group, six extra rats underwent bronchoalveolar lavage. Mean arterial pressure (MAP) and pulse oxygen saturation (SpO2) were recorded at each time point. The wet/dry weight ratio and lung permeability index (LPI) were measured. Quantitative RT-PCR and Western blot were used to measure pulmonary occludin and ZO-1, and Western blot was used to measure cytosolic and membranous PKC-alpha in the lung. Lung permeability was significantly increased after ischemia-reperfusion. Sevoflurane pretreatment promoted pulmonary expression of occludin and ZO-1 after reperfusion and inhibited the translocation of PKC-alpha. In conclusion, sevoflurane pretreatment alleviated lung permeability by upregulating occludin and ZO-1 after ischemia-reperfusion. Sevoflurane pretreatment inhibited the translocation and activation of PKC-alpha, which also contributed to the lung-protective effect of sevoflurane.
Anesthetics, Inhalation/*therapeutic use ; Animals ; Capillary Permeability/drug effects ; Gene Expression Regulation/drug effects ; Lung/*drug effects/metabolism/pathology ; Lung Diseases/*drug therapy/genetics/metabolism/pathology ; Male ; Methyl Ethers/*therapeutic use ; Protein Kinase C-alpha/*metabolism ; Protein Transport/drug effects ; RNA, Messenger/genetics ; Rats, Wistar ; Reperfusion Injury/*drug therapy/genetics/metabolism/pathology ; Zonula Occludens-1 Protein/analysis/*genetics

Several factors can affect the perioperative immune function. We evaluated the effect of propofol and desflurane anesthesia on the surgery-induced immune perturbation in patients undergoing breast cancer surgery. The patients were randomly assigned to receive propofol (n = 20) or desflurane (n = 20) anesthesia. The total and differential white blood cell counts were determined with lymphocyte subpopulations before and 1 hr after anesthesia induction and at 24 hr postoperatively. Plasma concentrations of interleukin (IL)-2 and IL-4 were also measured. Both propofol and desflurane anesthesia preserved the IL-2/IL-4 and CD4+/CD8+ T cell ratio. Leukocytes were lower in the propofol group than in the desflurane group at 1 hr after induction (median [quartiles], 4.98 [3.87-6.31] vs. 5.84 [5.18-7.94] 10(3)/microL) and 24 hr postoperatively (6.92 [5.54-6.86] vs. 7.62 [6.22-9.21] 10(3)/microL). NK cells significantly decreased 1 hr after induction in the propofol group (0.41 [0.34-0.53] to 0.25 [0.21-0.33] 10(3)/microL), but not in the desflurane group (0.33 [0.29-0.48] to 0.38 [0.30-0.56] 10(3)/microL). Our findings indicate that both propofol and desflurane anesthesia for breast cancer surgery induce a favorable immune response in terms of preservation of IL-2/IL-4 and CD4+/CD8+ T cell ratio in the perioperative period. With respect to leukocytes and NK cells, desflurane anesthesia is associated with less adverse immune responses than propofol anesthesia during surgery for breast cancer. (Clinical trial registration at https://cris.nih.go.kr/cris number: KCT0000939)
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anesthesia/adverse effects ; Anesthetics, Inhalation/*therapeutic use ; Anesthetics, Intravenous/*therapeutic use ; Breast Neoplasms/immunology/*surgery ; *CD4-CD8 Ratio ; Female ; Humans ; Interleukin-2/blood ; Interleukin-4/blood ; Isoflurane/*analogs & derivatives/therapeutic use ; Middle Aged ; Postoperative Period ; Propofol/*therapeutic use ; Young Adult

BACKGROUNDThe optimal ventilated status under total intravenous or inhalation anesthesia in neurosurgical patients with a supratentorial tumor has not been ascertained. The purpose of this study was to intraoperatively compare the effects of moderate hyperventilation on the jugular bulb oxygen saturation (SjO 2 ), cerebral oxygen extraction ratio (O 2 ER), mean arterial blood pressure (MAP), and heart rate (HR) in patients with a supratentorial tumor under different anesthetic regimens.

METHODSTwenty adult patients suffered from supratentorial tumors were randomly assigned to receive a propofol infusion followed by isoflurane anesthesia after a 30-min stabilization period or isoflurane followed by propofol. The patients were randomized to one of the following two treatment sequences: hyperventilation followed by normoventilation or normoventilation followed by hyperventilation during isoflurane or propofol anesthesia, respectively. The ventilation and end-tidal CO 2 tension were maintained at a constant level for 20 min. Radial arterial and jugular bulb catheters were inserted for the blood gas sampling. At the end of each study period, we measured the change in the arterial and jugular bulb blood gases.

RESULTSThe mean value of the jugular bulb oxygen saturation (SjO 2 ) significantly decreased, and the oxygen extraction ratio (O 2 ER) significantly increased under isoflurane or propofol anesthesia during hyperventilation compared with those during normoventilation (SjO 2 : t = -2.728, P = 0.011 or t = -3.504, P = 0.001; O 2 ER: t = 2.484, P = 0.020 or t = 2.892, P = 0.009). The SjO 2 significantly decreased, and the O 2 ER significantly increased under propofol anesthesia compared with those values under isoflurane anesthesia during moderate hyperventilation (SjO 2 : t = -2.769, P = 0.012; O 2 ER: t = 2.719, P = 0.013). In the study, no significant changes in the SjO 2 and the O 2 ER were observed under propofol compared with those values under isoflurane during normoventilation.

CONCLUSIONSOur results suggest that the optimal ventilated status under propofol or isoflurane anesthesia in neurosurgical patients varies. Hyperventilation under propofol anesthesia should be cautiously performed in neurosurgery to maintain an improved balance between the cerebral oxygen supply and demand.

Adolescent ; Adult ; Aged ; Anesthetics, Inhalation ; Anesthetics, Intravenous ; Arterial Pressure ; physiology ; Blood Gas Analysis ; Craniotomy ; methods ; Female ; Heart Rate ; physiology ; Humans ; Hyperventilation ; chemically induced ; physiopathology ; Isoflurane ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Propofol ; administration & dosage ; therapeutic use ; Young Adult

PURPOSE: 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). RESULTS: 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. CONCLUSION: Sevoflurane and desflurane can be used safely as volatile anesthetics in donors undergoing nephrectomy.
Adult ; Anesthesia, General/methods ; Anesthetics, Inhalation/adverse effects/*therapeutic use ; Female ; Humans ; Isoflurane/adverse effects/*analogs & derivatives/therapeutic use ; Kidney/*physiology ; Kidney Function Tests ; *Kidney Transplantation ; *Living Donors ; Male ; Methyl Ethers/adverse effects/*therapeutic use ; *Nephrectomy ; Postoperative Complications ; Retrospective Studies

PURPOSE: This study aims to investigate the most appropriate effect-site concentration of remifentanil to minimize cardiovascular changes during inhalation of high concentration desflurane. MATERIALS AND METHODS: Sixty-nine American Society of Anesthesiologists physical status class I patients aged 20-65 years were randomly allocated into one of three groups. Anesthesia was induced with etomidate and rocuronium. Remifentanil was infused at effect-site concentrations of 2, 4 and 6 ng/mL in groups R2, R4 and R6, respectively. After target concentrations of remifentanil were reached, desflurane was inhaled to maintain the end-tidal concentration of 1.7 minimum alveolar concentrations for 5 minutes (over-pressure paradigm). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and end-tidal concentration of desflurane were measured for 5 minutes. RESULTS: The end-tidal concentration of desflurane increased similarly in all groups. The SBP, DBP, MAP and HR within group R4 were not significantly different as compared with baseline values. However, measured parameters within group R2 increased significantly 1-3 minutes after desflurane inhalation. The MAP within group R6 decreased significantly at 1, 2, 4, and 5 minutes (p<0.05). There were significant differences in SBP, DBP, MAP and HR among the three groups 1-3 minutes after inhalation (p<0.05). The incidence of side effects such as hyper- or hypo-tension, and tachy- or brady-cardia in group R4 was 4.8% compared with 21.8% in group R2 and 15.0% in group R6. CONCLUSION: The most appropriate effect-site concentration of remifentanil for blunting hemodynamic responses by inhalation of high concentration desflurane is 4 ng/mL.
Adult ; Aged ; Androstanols/adverse effects/pharmacology ; Anesthetics/adverse effects/pharmacology ; Anesthetics, Inhalation/adverse effects/*pharmacology ; Blood Pressure/drug effects ; Etomidate/adverse effects/pharmacology ; Female ; Heart/*drug effects ; Heart Rate/drug effects ; Humans ; Isoflurane/adverse effects/*analogs & derivatives/pharmacology ; Male ; Middle Aged ; Piperidines/adverse effects/*therapeutic use ; Protective Agents/adverse effects/*therapeutic use

BACKGROUNDInhalational anesthesia with sevoflurane for endotracheal intubation without muscle relaxant is now used widely for pediatric patients. This study assessed the efficacy and safety of induction with high concentration sevoflurane and of nasotracheal intubation without muscle relaxant in infants with increased or decreased pulmonary blood flow (PBF) and undergoing surgery for congenital heart diseases.

METHODSFifty-five infants aged 2 - 12 months, weighing 4.7 - 10.0 kg, and scheduled for congenital cardiac surgery were enrolled. Subjects were divided into those with increased (IPBF group, n = 29) and decreased (DPBF group, n = 26) pulmonary blood flow. All infants received inhalational induction with 8% sevoflurane in 100.0% oxygen at a gas flow rate of 6 L/min. Nasotracheal intubation was performed 4 minutes after induction. Sevoflurane vaporization was decreased to 4.0% for placement of a peripheral intravenous line and invasive hemodynamic monitors. Five minutes later, sedatives and muscle relaxant were administered and the vaporizer was adjusted to 2% for maintenance of anesthesia. Bispectral index (BIS) scores, circulatory parameters, satisfactory and successful intubation ratios, adverse reactions, and complications of intubation were recorded.

RESULTSTimes to loss of lash and pain reflexes were longer for the DPBF group (P < 0.01). Satisfactory intubation ratios were 93.1% and 61.5% for the IPBF and DPBF groups, respectively (P = 0.008). Successful intubation ratios were 96.6% and 76.9% for the IPBF and DPBF groups, respectively (P = 0.044). Following sevoflurane inhalation, blood pressures decreased significantly in the IPBF group but remained stable in the DPBF group. BIS scores declined to similar stable values, and a "nadir BIS" was recorded for both groups. No obvious adverse reactions or complications of intubation were noted perioperatively.

CONCLUSIONSInduction with high concentration sevoflurane, although faster for infants with IPBF, is safe for infants with IPBF or DPBF. However, nasotracheal intubation without muscle relaxant after induction with high concentration sevoflurane is less successful and less satisfactory for infants with DPBF and should be used with caution in this patient group.

Anesthetics, Inhalation ; Blood Circulation ; drug effects ; Female ; Heart Defects, Congenital ; surgery ; Humans ; Infant ; Intubation, Intratracheal ; Lung ; blood supply ; drug effects ; Male ; Methyl Ethers ; therapeutic use

OBJECTIVETo compare the effect and hemodynamics of sevoflurane(SEV) and propofol (PRO) in combined anesthesia induction with remifentanil for tracheal intubation fibreoptic bronchoscope (FOB).

METHODSTwenty-four patients without difficult airway undergoing elective surgery with tracheal intubation general anesthesia were randomly divided into SEV and PRO group. FOB intubation was performed with sevoflurane or propofol administration combined with remifentanil induction. Blood pressure (BP), heart rate (HR), SPO2 and Narcotrend index (NI) were monitored to evaluate the anesthetic depth during the induction. The time to loss of consciousness (LOC), intubation time, intubation score, anesthetic dosage and adverse effects were recorded.

RESULTSNo significant difference was found between the two groups in the time to LOC, intubation time, intubation score, remifentanil dosage. Intubation was performed successfully in both groups. BP and HR of both groups decreased after the induction and did not increase after the intubation, with variation within the normal range. No significant difference in BP and HR was found between the two groups. NI of both groups decreased after the induction and during intubation. NI of SEV group 2 min after intubation was higher than that of PRO group. There was no significant difference in NI between the two groups at the other time points. No significant adverse effects or recall of the intubation procedure were reported.

CONCLUSIONAnesthesia induction FOB intubation with sevoflurane and propofol, both in combination with remifentanil, can be applied in surgical patients without contraindications to general anesthesia, and both methods can provide fast induction and good intubation condition with stable hemodynamics.

Adult ; Aged ; Anesthesia ; methods ; Anesthetics, Inhalation ; therapeutic use ; Anesthetics, Intravenous ; therapeutic use ; Bronchoscopes ; Hemodynamics ; Humans ; Intubation, Intratracheal ; methods ; Methyl Ethers ; therapeutic use ; Middle Aged ; Piperidines ; therapeutic use ; Propofol ; therapeutic use

BACKGROUNDStudies suggested that anesthetics administered upon the early reperfusion or "anesthetic postconditioning" could protect post-ischemic hearts against myocardial ischemia reperfusion injury (MIRI). However, the mechanism responsible for such protection was not well-elucidated. We investigated the cardioprotection induced by sevoflurane postconditioning (SpostC) in rat hearts in vitro, and the respective role of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase 1 and 2 (ERK 1/2), mitochondrial K(ATP) channels (mitoK(ATP)) and mitochondrial permeability transition pore (mPTP), by selectively inhibiting PI3K, ERK 1/2, mitoK(ATP), with LY294002 (LY), PD98059 (PD), 5-hydroxydecanoate (5-HD) and by directly opening of mPTP with atractyloside (ATR), respectively.

METHODSIsolated rat hearts were randomly assigned to one of the 12 groups (n = 15): Time control (continuous perfusion), ISCH (30 minutes of ischemia followed by 60 minutes of reperfusion alone), SpostC (3% sevoflurane postconditioning was administered during the first 15 minutes of reperfusion after 30 minutes of ischemia), ISCH + LY, ISCH + PD, ISCH + ATR, ISCH + 5-HD and ISCH + dimethyl sulfoxide (DMSO) groups (LY, PD, ATR, 5-HD and DMSO (the vehicle) was administered respectively during the first 15 minutes of reperfusion following test ischemia), SpostC + LY, SpostC + PD, SpostC + ATR and SpostC + 5-HD groups (LY, PD, ATR and 5-HD was coadministered with 3% sevoflurane, respectively). Hemodynamics was compared within and between groups. Infarction size was determined at the end of experiments using triphenyltetrazolium chloride (TTC) staining. Lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) released from necrotic myocardium, were compared among TC, ISCH and SpostC groups. To investigate the relationships between RISK and mPTP implicated in SpostC, NAD(+) content in myocardium, a marker of mPTP opening, was compared among some experimental groups (TC, ISCH, ISCH + LY, ISCH + PD, ISCH + DMSO, SpostC, SpostC + LY, SpostC + PD). To further investigate whether the anti-apoptotic mechanism is implicated in SpostC-induced cardioprotection and its association with mitochondria, TUNEL staining was performed in some experimental groups (TC, ISCH, ISCH + 5-HD, ISCH + ATR, ISCH + DMSO, SpostC, SpostC + 5-HD, SpostC + ATR).

RESULTSWhen compared with unprotected hearts subjected to 30 minutes of ischemia, exposure to 3% sevoflurane for 15 minutes during early reperfusion significantly improved functional recovery, decreased myocardial infarct size, decreased LDH, CK-MB and cTnI release, and decreased cardiomyocyte apoptosis (P < 0.05). However, such cardioprotective effects of hemodynamic recovery and infarct size reduction by sevoflurane was completely abolished by any one of LY294002, PD98059, atractyloside and 5-hydroxydecanoate (P < 0.05). Additionally, either LY294002 or PD98059 could reverse the inhibitory effect of SpostC over mPTP opening upon reperfusion (P < 0.05). Both atractyloside and 5-hydroxydecanoate could abrogate the anti-apoptotic effects of SpostC (P < 0.05).

CONCLUSIONThese findings demonstrate that PI3K, ERK 1/2, mitoK(ATP) and mPTP are key players in sevoflurane postconditioning induced cardioprotective mechanisms in isolated rat hearts subjected to MIRI.

Anesthetics, Inhalation ; therapeutic use ; Animals ; Apoptosis ; drug effects ; Heart ; drug effects ; Male ; Methyl Ethers ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control

BACKGROUNDThe mechanisms of action of volatile anesthetics are still unknown. Recently, the use of genetics as a means to investigate anesthetic action has increased in scale. However, only limited forward genetic approach studies were performed in mammals, especially with volatile anesthetics as the selection agent. In the present study, a selective breeding process was designed to produce strains of mice with different sensitivity to isoflurane.

METHODSOne hundred and sixty male and female virgin outbred ICR/CD-1 mice at 65 - 70 days of age were selected as original generation, and the median effective dose (ED(50)) of inhaled isoflurane were measured by probit analysis with the loss of righting reflex as the endpoint of anesthesia. The most sensitive males and females were selected and mated one another randomly, as with the most resistant males and females. Thus two branches of mice (sensitive and resistant to isoflurane) were created and allowed to produce the next generation. At 65 - 70 days of age, screening experiment was performed in offspring, by selecting the most sensitive mice in sensitive branch and the most resistant mice in resistant branch. Selected males and females within each branch were mated one another randomly to produce the following generation. The same procedure was performed in the offspring. The process of screening and breeding was repeated for 8 generations, and then strains were conserved by mating the offspring one another randomly within each branch for 3 generations. Each pair of mice was allowed to produce the second litters as a backup, and isoflurane ED(50) was measured in mice from the second litters.

RESULTSIsoflurane righting reflex ED(50)s (95% confidence limit (CL)) in original mice were 0.65% (0.58% - 0.72%) in females and 0.63% (0.56% - 0.69%) in males. After the 4th generation, isoflurane ED(50)s in resistant branch were significantly higher than those in sensitive branch (P < 0.05), for both in females and males. In the 11th generation, isoflurane ED(50) in the two branches differed by 32% in females and 36% in males.

CONCLUSIONSAfter 8 generations of selective breeding and 3 generations of strain conservation, two strains of mice with high and low sensitivity to isoflurane were developed. The separation of inhaled anesthetic requirement in parents could be transferred to the offspring in mice.

Anesthetics, Inhalation ; therapeutic use ; Animals ; Breeding ; methods ; Female ; Isoflurane ; therapeutic use ; Male ; Mice ; Mice, Inbred ICR ; Reflex ; drug effects ; Selection, Genetic ; genetics