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We evaluated the minimum alveolar concentration of sevoflurane required to maintain the bispectral index below 50 in children. We studied 55 children, divided into 1-year-old, 2- to 4-year-old and 5- to 9-year-old groups and used Dixon's up-and-down method and probit analysis. In the 1-year-old group, the bispectral index values remained above 50, with the end-tidal sevoflurane concentration reaching 4.0% or higher. The minimum alveolar concentration of sevoflurane for maintaining the bispectral index below 50 was significantly higher in the 2- to 4-year-old group (2.33%, 95% CI 2.25-2.57) than in the 5- to 9-year-old group (2.10%, 95% CI 1.94-2.25; p = 0.005). We conclude that assessing the depth of anaesthesia using bispectral index is unreliable in children aged < 2 years anaesthetised with sevoflurane., (© 2014 The Association of Anaesthetists of Great Britain and Ireland.)

Objective: To determine minimum alveolar concentration (MAC) of sevoflurane for maintaining bispectral index (BIS) below 50 (MAC(BIS50) ) in children., Background: MAC(BIS50) of sevoflurane in adults was reported to be 0.97%, which has not been elucidated in children., Methods/materials: Twenty children, American Society of Anesthesiologists physical status I or II, aged 1-8, were induced and anesthetized with sevoflurane in oxygen. After tracheal intubation, we started maintenance of anesthesia with endtidal sevoflurane concentrations of 2.6%. The endtidal sevoflurane concentration at which BIS was measured was predetermined by the up-down method (with 0.2% as a step size). After 10 min at predetermined endtidal sevoflurane concentrations, BIS was measured for 1 min. MAC(BIS50) was determined using Dixon's up-down method and probit test., Result: MAC(BIS50) of sevoflurane was 2.83% (95% confidence intervals: 2.70-3.14) in children., Conclusions: MAC(BIS50) of sevoflurane in children was calculated to be three times as high as in adults. This indicates that high endtidal sevoflurane concentration is required to suppress electroencephalogram activity in children., (© 2011 Blackwell Publishing Ltd.)

Background: Sevoflurane can be used as a sole agent for intubation in children, but studies have suggested that it is associated with emergence agitation. Fentanyl infusions can be used both to facilitate intubation and decrease emergence agitation. We investigated the effects of fentanyl on conditions at intubation and on emergence from sevoflurane anaesthesia without confounding nitrous oxide or premedication., Methods: IRB approval and informed consent were obtained. Subjects comprised 150 ASA physical status I or II (age, 2-6 yr). Anaesthesia was induced with sevoflurane in oxygen and maintained using a predetermined concentration of sevoflurane. Subjects were randomly allocated to receive one of three doses of fentanyl: vehicle only (control group), a bolus dose of 1 microg kg(-1) followed by a continuous infusion of 0.5 microg kg(-1) h(-1) (F1 group), or a bolus dose of 2 microg kg(-1) followed by a continuous infusion of 1 microg kg(-1) h(-1) (F2 group). Sevoflurane minimum alveolar concentration for tracheal intubation (MAC(TI)) and emergence agitation score were assessed., Results: MAC(TI) values were 2.49%, 1.61%, and 1.16% in control, F1, and F2 groups, respectively (P<0.05). Agitation scores were 11.5, 7.0, and 2.6 in control, F1, and F2 groups, respectively (P<0.05)., Conclusions: Fentanyl infusion consisting of a bolus dose of 2 microg kg(-1) followed by a continuous infusion of 1 microg kg(-1) h(-1) facilitates tracheal intubation and smooth emergence in children anaesthetized using sevoflurane., Clinical Trial Registration: this study was started in 2000 and was finished in 2008. We had no registration number. IRB approval was obtained.

Background: Progesterone has long been known to have central effects, by reduced anaesthetic requirements as measured by minimum alveolar concentration (MAC) in various settings. However, other studies have contradicted these findings. Therefore, we compared the effect of progesterone on anaesthetic requirements in a mouse model., Methods: Male C57BL/6 mice were treated with either progesterone (37.5 or 75 mg kg(-1)) or the olive oil vehicle, 1 h before each experiment. Animals were placed in a revolving cylinder (4 rev min(-1)) and supplied with oxygen and stepwise increasing concentrations of sevoflurane. The number of complete rollovers during revolution of the chamber was counted as a measure of anaesthetic requirement., Results: S.C. administration of progesterone 75 mg kg(-1) significantly reduced sevoflurane requirement (P<0.0001). Progesterone 37.5 mg kg(-1) did not change sevoflurane requirement., Conclusions: We conclude that administration of exogenous progesterone injection at higher concentrations decreases anaesthetic requirement as defined by rolling response.

Background: Inhalational induction with sevoflurane and nitrous oxide is frequently used for Laryngeal Mask Airway (LMA; Laryngeal Mask Company, Henley-on-Thames, United Kingdom) insertion in children. The authors determined the influence of nitrous oxide on the minimum alveolar concentration (MAC) of sevoflurane for LMA insertion., Methods: One hundred twenty unpremedicated children (age, 1-9 yr; American Society of Anesthesiologists physical status I) were randomly assigned to receive 1 of 15 end-tidal concentrations of nitrous oxide and sevoflurane for inhalational induction via a facemask: 0% nitrous oxide with 1.2, 1.4, 1.6, 1.8, or 2.0% sevoflurane; 33% nitrous oxide with 0.8, 1.0, 1.2, 1.4, or 1.6% sevoflurane; or 67% nitrous oxide with 0.4, 0.6, 0.8, 1.0, or 1.2% sevoflurane. The LMA was inserted after steady state end-tidal anesthetic concentrations had been maintained for 15 min. The response to insertion was recorded by three independent blinded observers. The interaction between nitrous oxide and sevoflurane was determined using logistic regression analysis., Results: The MAC of sevoflurane for LMA insertion (95% confidence limit) was 1.57% (1.42-1.72%), and the concentration of sevoflurane required to prevent movement in 95% of children was 1.99% (1.81-2.57%). The addition of 33% and 67% nitrous oxide linearly decreased the MAC of sevoflurane for LMA insertion by 22% and 49%, respectively (P < 0.001). The interaction coefficient between nitrous oxide and sevoflurane did not differ from zero (P = 0.7843), indicating that the relation was additive., Conclusions: Nitrous oxide and sevoflurane suppress the responses to LMA insertion in a linear and additive fashion in children.

Unlabelled: Although clonidine has both hypnotic and analgesic actions, the dose relationship for each actions is still unknown in a clinical setting when clonidine is used as a premedication in children. We studied 80 ASA physical status I children (age range, 3-8 yr). Subjects were randomly divided into two groups (minimum alveolar anesthetic concentration [MAC]-Awake group, n = 40; MAC-Tetanus group, n = 40). Each patient received one dose of clonidine from 1 to 5 microg/kg orally, 100 min before arrival at the operating room. Anesthesia was induced and maintained with sevoflurane in oxygen and air. Before tracheal intubation, end-tidal sevoflurane was decreased stepwise by 0.2% at the start of 1.2%, a verbal command was given to the patients, and MAC-awake was determined in each patient. We also investigated MAC-tetanus, determined with transcutaneous electric tetanic stimulations, after tracheal intubation in each patient by observing the motor response to a transcutaneous electric tetanic stimulus to the ulnar nerve at a sevoflurane concentration decreased stepwise by 0.25% at the start of 2.75%. The initial reduction in MAC-tetanus was not as steep as that in MAC-awake. Clonidine reduced MAC-tetanus by 40% at the maximal dose of 5 microg/kg, whereas MAC-awake was already reduced by 50% at 2 microg/kg. We conclude that separate dose-response relationships for oral clonidine are present regarding the hypnotic and analgesic effects in children undergoing sevoflurane anesthesia., Implications: Separate dose-response relationships for oral clonidine were found regarding the hypnotic and analgesic effects in children undergoing sevoflurane anesthesia.

Unlabelled: The effects of clonidine on minimum alveolar concentration for tracheal extubation (MAC-ex) have not been elucidated. Clonidine may lead to prolonged emergence from anesthesia. We investigated the effects of oral clonidine premedication on MAC-ex and examined the emergence properties of sevoflurane in children. Sixty ASA physical status I pediatric patients, aged from 2 to 9 yr, were randomly divided into one of three groups and received placebo, clonidine 2 microg/kg, or clonidine 4 microg/kg (n = 20 each) orally, 100 min before the induction of anesthesia. The induction of anesthesia, tracheal intubation, and maintenance of anesthesia were performed with sevoflurane in air and oxygen. MAC-ex was defined according to the modification of Dixon's up-and-down method, with 0.25% as a step size. In addition, in the Control and 4 microg/kg groups, the time from tracheal extubation to spontaneous eye opening (eye-opening time) and the time from tracheal extubation to leaving the operating room (awakening time) were recorded. MAC-ex for sevoflurane (mean +/- SD) was 1.63% +/- 0.13%, 1.04% +/- 0.26%, and 0.66% +/- 0.09% respectively in the Control group, 2 microg/kg group, and 4 microg/kg group. Significant differences were observed among the three groups. The eye-opening times were 5.7 +/- 3.5 min in the Control group and 5.1 +/- 1.0 min in the 4 microg/kg group. The awakening times were 9.7 +/- 3.7 min in the Control group and 9.2 +/- 3.8 min in the 4 microg/kg group. No significant differences were observed among the groups., Implications: Oral clonidine premedication decreased MAC for tracheal extubation for sevoflurane dose dependency and did not prolong emergence from anesthesia.

We examined the relative effects of different doses of oral clonidine on the MAC for endotracheal intubation (MACEI) and the MAC for skin incision (MAC) in children. We studied 90 children (15 in each group) (age range 2-8 yr, weight 10-27 kg, height 89-124 cm) who received one of three preanaesthetic medications: placebo (control), oral clonidine 2 micrograms kg-1, or oral clonidine 4 micrograms kg-1 100 min before anaesthesia. Anaesthesia was induced and maintained with sevoflurane in oxygen and air without i.v. anesthetics and neuromuscular relaxants. The end-tidal sevoflurane concentration was kept constant for > or = 15 min before tracheal intubation or skin incision. MACs were determined using Dixon's 'up-and-down method'. Mean (SD) MACEIs of sevoflurane were 2.9 (0.1)%, 2.5 (0.1)% and 1.9 (0.1)% (P < 0.05), and MACs were 2.3 (0.1)%, 1.8 (0.1)% and 1.3 (0.1)% (P < 0.05), respectively, in control, clonidine 2 micrograms kg-1 and clonidine 4 micrograms kg-1 groups. The MACEIs and MACs decreased dose-dependently. The MACEI/MAC ratio (1.4) was not affected by clonidine.

Unlabelled: Sevoflurane is frequently used as a rapidly acting drug for the induction of anesthesia. We investigated the awakening concentration (MAC-awake) of sevoflurane in ASA physical status I children (age range 2-10 yr). We also investigated the effects of two different doses of clonidine (2 and 4 microg/kg) on the MAC-awake of sevoflurane. Subjects were randomly divided into three groups and received placebo (n = 24), clonidine 2 microg/kg (n = 17), or clonidine 4 microg/kg (n = 22) orally, 100 min before the induction of anesthesia. Sedation scores were estimated, by using a five-point scale, after entry into the operating room, and anesthesia was induced and maintained with sevoflurane in oxygen and balanced nitrogen, without an additional anesthetic. After surgery, end-tidal sevoflurane was decreased stepwise by 0.2% at 15-min intervals, a standardized verbal command was played to the patients, and the MAC-awake was determined. The MAC-awake of sevoflurane alone was 0. 78% +/- 0.24% (mean +/- SD), which decreased to 0.36% +/- 0.09% and 0.36% +/- 0.16% (both P <0.0001, compared with the control group) after premedication with the small and large doses of clonidine, respectively. The lack of any dose-response relationship might be explained by a plateau effect., Implications: The awakening concentration of sevoflurane in unpremedicated children was 0.78%. Oral clonidine premedication at a dose of 2 microg/kg reduced the awakening concentration to 0.36%. However, an additional decrease in this value was not observed after the administration of the larger dose of clonidine premedication (4 microg/kg).

Unlabelled: We assessed the effects of oral clonidine preanesthetic medication (4.5 microg/kg) on the vital capacity rapid-inhalation anesthetic induction time (VCRII time) and minimum alveolar anesthetic concentration (MAC) to prevent a response to a verbal command in 50% of patients (MAC-Awake) by its hypnotic effect, and on MAC-Skin incision for the analgesic effect in patients anesthetized with sevoflurane. We studied 104 adult patients (control group: n = 52, clonidine group: n = 52) aged 30-48 yr scheduled to undergo general anesthesia. Fifty-two patients received oral clonidine 4.5 microg/kg 1.5 h before arrival in the operating room (clonidine group). The patients exhaled to residual volume and took three vital capacity breaths of 5% sevoflurane in oxygen. The VCRII time was defined as the time interval between the initiation of the VCRII and the disappearance of the response to verbal command. Anesthesia was maintained with sevoflurane in oxygen and air. The end-tidal (ET) sevoflurane concentration reached a predetermined value, then the ratio of predetermined ET to inspiratory concentration was maintained at > or =0.95 for at least 15 min before skin incision. After skin incision, the patients were observed for gross purposeful muscular movements. MAC was defined as the average of the cross-over midpoints in each cross-over. After maintaining the ET sevoflurane concentration for 15 min, patients were judged to be awake or asleep. Average times for VCRII using 5% sevoflurane were achieved in 44+/-11 s (mean +/- SD) and 27+/-6 s in the control and clonidine groups, respectively (P = 0.0001). MAC-Awake values of sevoflurane were 0.66%+/-0.03% and 0.35%+/-0.02% (P = 0.0001), and MAC-Skin incision values were 1.97%+/-0.19% and 1.29%+/-0.13% (P = 0.0001) in the control and clonidine groups, respectively. These results suggest that clonidine may have a more potent hypnotic effect than analgesic effect., Implications: Oral clonidine preanesthetic medication (4.5 microg/kg) significantly reduces vital capacity rapid inhalation anesthetic induction time and minimum alveolar anesthetic concentration awake for sevoflurane.

Sevoflurane has a non-pungent odour and provides smooth induction of anaesthesia. In contrast, isoflurane is irritating to the airway when used for induction, and this may also be evident during emergence from anaesthesia. We measured the end-tidal concentration of anaesthetic that prevented response to extubation in 50% of patients (MACEX) in adults receiving either sevoflurane or isoflurane. Airway complications during emergence from anaesthesia were also noted. We studied 51 adult patients, ASA 1, aged 36-59 yr. Patients received sevoflurane (n = 29) or isoflurane (n = 22) for elective intraocular surgery. The concentration at which extubation was attempted was determined by a modification of Dixon's up-and-down method. When tracheal extubation was accomplished without coughing and gross purposeful muscular movements within 1 min after extubation, it was considered a smooth tracheal extubation. Patients who developed breath-holding or laryngospasm immediately after tracheal extubation were regarded as not having been extubated smoothly. In addition, patients were observed for respiratory events during the remainder of the emergence period. MACEX values for sevoflurane and isoflurane were 1.07% and 0.83%, respectively. ED95 values of sevoflurane and isoflurane were 2.04% and 1.19%, respectively. In 12 patients in the isoflurane group, extubation was smooth but six patients had coughing episodes during the remainder of the emergence period. In contrast, one of 15 patients in the sevoflurane group in whom tracheal extubation was smooth coughed later (P = 0.035). Airway obstruction was frequent when tracheal extubation was performed at end-tidal concentrations exceeding 1 MACEX for each anaesthetic.

Unlabelled: We sought to determine minimum alveolar anesthetic concentrations for skin incision (MAC) and for tracheal extubation (MAC(Ex)) for sevoflurane and its associated awakening time and respiratory complications during emergence from sevoflurane anesthesia in children. We studied 40 (20 in each group) unpremedicated pediatric patients ranging in age from 2 to 8 yr. For MAC(Ex) determination, anesthetic induction, tracheal intubation, and maintenance of anesthesia were performed with sevoflurane and N2O in oxygen. However, N2O administration was discontinued at the end of surgery. The ratio of the predetermined end-tidal to inspiratory concentration was maintained at 0.95-1.00 for at least 15 min. The trachea was gently extubated, and smooth tracheal extubation was defined by the absence of gross purposeful muscular movements. In addition, the respiratory complications and awakening time were investigated during emergence from anesthesia for each patient. For MAC determination, anesthesia induction and tracheal intubation were performed with 5% sevoflurane in oxygen. After the predetermined end-tidal sevoflurane concentration had been established and maintained for at least 15 min, skin incision was attempted. Patients' responses to skin incision were described as "no movement" or "movements." The MAC or MAC(Ex) for sevoflurane was 2.22% +/- 0.13% (mean+/-SD) or 1.70%+/-0.12%, and the 95% effective dose (ED95) for smooth extubation was 1.87% (95% confidence limits 1.75%-2.62%), respectively, in children. During emergence from anesthesia, none of patients held their breath or experienced laryngospasm in the current study. One patient in a subgroup at 1.5% coughed before tracheal extubation. All 10 patients with smooth tracheal extubation had hemoglobin oxygen saturation levels of > or =98% in this study. Awakening time was 9.7+/-3.7 min in the subgroup that received 1.75% sevoflurane. In conclusion, the MAC(Ex) and ED95 values of sevoflurane were 1.64% and 1.87%, respectively, in children. The MAC(Ex) to MAC ratio for sevoflurane was 0.8 in children within the same age range and mean age., Implications: Because tracheal extubation of anesthetized patients may be advantageous in certain clinical situations, we performed this study. The ratio minimum alveolar anesthetic concentrations for skin incision and for tracheal extubation for sevoflurane was 0.8 in children within the same age range and mean age. No patient in the current study had laryngospasm.

The current study was designed to determine the anaesthetic induction time required for tracheal intubation (TimeEI) with equipotent inspired concentrations of 5% sevoflurane and 2.5% halothane in oxygen. TimeEI that prevents 50% and 95% of patients from coughing and gross purposeful muscular movements after intubation was defined as TimeEI50 and TimeEI95, respectively. Thirty-six patients aged 1-7 years were enrolled in the study. Anaesthesia was induced via mask and when TimeEI attained a predetermined value, intubation was performed using an uncuffed tube. Each TimeEI at which tracheal intubation was attempted was predetermined according to the up-and-down method. When intubation was accomplished without gross purposeful muscular movements, it was considered a smooth intubation. Determination with this method revealed that TimeEI50 and TimeEI95 for the sevoflurane/halothane groups were 147/214 s and 194/255 s, respectively. In conclusion, it is possible to determine TimeEI using an inspired sevoflurane concentration of 5% and halothane 2.5% in oxygen. The technique with 5% sevoflurane seems more practical for paediatric anaesthesia induction in busy clinical situations.

Purpose: Using the conventional method of determining the end-tidal concentration of inhalational anaesthetic for tracheal intubation, a constant end-tidal anaesthetic concentration is maintained for at least 15 min. As sevoflurane has a low tissue/gas partition coefficient, it seems possible in paediatric patients to determine end-tidal concentrations for tracheal intubation more rapidly by using a high inspired concentration. We determined ED50 and ED95 of sevoflurane for tracheal intubation, the end-tidal concentrations that prevented 50% and 95% of patients from coughing and gross purposeful muscular movements after intubation., Methods: Twenty-nine, ASA 1, unpremedicated patients, aged two to eight years, were enrolled. Anaesthesia was induced using a mask and 5% sevoflurane, inspired, in oxygen. When end-tidal sevoflurane concentration attained a predetermined value, laryngoscopy and tracheal intubation were performed using an uncuffed tracheal tube without neuromuscular relaxants or adjuvants. Each concentration at which laryngoscopy and tracheal intubation were attempted was randomly predetermined (with 0.5% as a step size). When tracheal intubation was accomplished without gross purposeful muscular movements, it was considered a smooth tracheal intubation., Results: The ED50 end-tidal sevoflurane concentration for tracheal intubation was 3.10% (95% confidence limits: 2.43% and 3.78%), and the ED95 was 4.68% (95% confidence limits: 3.91% and 12.74%). The times to end-tidal sevoflurane concentrations of 3.0% and 4.5% were 149 +/- 15 sec (mean +/- SD) and 213 +/- 23 sec., Conclusion: In paediatric patients, this method enabled determination of ED50 and ED95 end-tidal sevoflurane concentrations for tracheal intubation without obtaining a long stabilization period.

Background: Sevoflurane, a new inhalational anesthetic agent characterized by a low blood-gas partition coefficient and nonpungent odor, appears suitable as an induction agent for children. The laryngeal mask airway is a new device for maintaining airway patency during anesthesia. This study was conducted to determine the sevoflurane concentrations required for insertion of a laryngeal mask (MACLMI) and for tracheal intubation (MACTI) in children., Methods: Forty-two patients, aged 1-9 yr, scheduled for surgery during general anesthesia were randomly assigned into two groups: MACLMI (n = 21) and MACTI (n = 21). After the predetermined end-tidal concentration had been established and maintained for 20 min, laryngeal mask insertion or tracheal intubation was attempted without neuromuscular relaxants or other adjuvants. Each concentration at which laryngeal mask insertion or tracheal intubation was attempted was predetermined by the up-and-down method (with 0.5% as a step size)., Results: Sevoflurane MACLMI was 2.00 +/- 0.28%. Sevoflurane MACTI was 2.83 +/- 0.34%, significantly greater than MACLMI., Conclusions: Laryngeal mask insertion can be performed at a lesser sevoflurane concentration than that required for tracheal intubation.

The purpose of this study was to determine both the concentration of sevoflurane required for tracheal intubation (MACEI) and its minimum alveolar anesthetic concentration (MAC) in adults. The study group consisted of 86 elective surgical patients, ASA physical status I or II, aged 16-59 yr. There was no premedication administered. For MACEI determination, after establishing and maintaining the predetermined end-tidal concentration for 20 min, tracheal intubation was attempted using a cuffed tracheal tube without muscle relaxant or other adjuvants. Each concentration at which tracheal intubation was attempted was predetermined as follows: 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, and 7.0%. For MAC determination, the patients examined were basically the same as those for MACEI determination, except for those who received muscle relaxant or other adjuvants because they were "not intubated smoothly." After establishing and maintaining the predetermined end-tidal concentration for 20 min, skin incision was attempted. Each concentration at which skin incision was attempted was predetermined as follows: 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, and 3.0%. The MACEI of sevoflurane was 4.52% (95% confidence limits, 3.91%-5.21%), and the ED95 for tracheal intubation was 8.07%. The MAC of sevoflurane was 1.58% (95% confidence limits, 1.14%-1.98%), and the AD95 (anesthetic ED95) was 2.96%. The MACEI/MAC ratio was 2.86 (95% confidence limits, 2.63-3.43). Anesthesia induction followed by tracheal intubation can be accomplished in adults when sevoflurane is administered as a sole anesthetic, but in excess of 8% end-tidal concentration.

Background: Sevoflurane is a new inhalational anesthetic agent having low solubility in blood and a relatively nonpungent odor. As such it should be useful as an inhalation induction in pediatric patients. The objectives of the study were to determine both the minimum alveolar concentration (MAC) and the concentration required for tracheal intubation (MACEI) of sevoflurane in pediatric patients., Methods: The study group consisted of 36 ASA physical status 1 elective surgical patients, aged 1-9 yr. MACEI determination: After establishing and maintaining the end-tidal concentration for 15 min, tracheal intubation was attempted with an uncuffed tracheal tube without neuromuscular relaxants or other adjuvants. Each concentration at which tracheal intubation was attempted was predetermined according to the up-and-down method (with 0.5% as a step size). MAC determination: The patients examined were the same as those for MACEI determination except that for the exclusion of those to whom neuromuscular relaxants or other adjuvants drugs were administered. End-tidal sevoflurane concentration was determined according to the up-and-down method (with 0.5% as a step size) and held constant for at least 15 min before a skin incision., Result: MACEI of sevoflurane was 2.69% (95% fiducial limits: 2.23% and 3.37%); MAC of sevoflurane was 2.03% (95% fiducial limits: 1.51% and 2.53%); and the MACEI/MAC ratio was 1.33., Conclusion: Sevoflurane appears to be suitable for use in pediatric patients as an induction agent, permitting tracheal intubation without neuromuscular relaxants.