Induction, Recovery, and Safety Characteristics of Sevoflurane in Children Undergoing Ambulatory Surgery: A Comparison with Halothane

Background: Sevoflurane is an inhalational anesthetic with characteristics suited for use in children. To determine whether the induction, recovery, and safety characteristics of sevoflurane differ from those of halothane, the following open-labeled, multicenter, randomized, controlled, phase III study in children undergoing ambulatory surgery was designed.

Methods: Three hundred seventy-five children, ASA physical status 1 or 2, were randomly assigned in a 2:1 ratio to receive either sevoflurane or halothane, both in 60% N2 O and 40% O2. Anesthesia was induced using a mask with an Ayre's t piece or Bain circuit in four of the centers and a mask with a circle circuit in the fifth center. Maximum inspired concentrations during induction of anesthesia were 7% sevoflurane and 4.3% halothane. Anesthesia was maintained by spontaneous ventilation, without tracheal intubation. End-tidal concentrations of both inhalational anesthetics were adjusted to 1.0 MAC for at least 10 min before the end of surgery. Induction and recovery characteristics and all side effects were recorded. The plasma concentration of inorganic fluoride was measured at induction of and 1 h after anesthesia.

Results: During induction of anesthesia, the time to loss of the eyelash reflex with sevoflurane was 0.3 min faster than with halothane (P < 0.001). The incidence of airway reflex responses was similar, albeit infrequent with both anesthetics. The total MAC *symbol* h exposure to sevoflurane was 11% less than the exposure to halothane (P < 0.013), although the end-tidal MAC multiple during the final 10 min of anesthesia was similar for both groups. Early recovery as evidenced by the time to response to commands after sevoflurane was 33% more rapid than it was after halothane (P < 0.001), although the time to discharge from hospital was similar for both anesthetics. The mean (+/-SD) plasma concentration of inorganic fluoride 1 h after discontinuation of sevoflurane was 10.3+/-3.5 micro Meter. The overall incidence of adverse events attributable to sevoflurane was similar to that of halothane, although the incidence of agitation attributable to sevoflurane was almost threefold greater than that attributable to halothane (P < 0.004).     

Induction of Anesthesia and Tracheal Intubation with Sevoflurane in Adults

Background: The speed, quality, and cost of mask induction of anesthesia and laryngeal mask airway insertion or tracheal intubation were studied in young non-premedicated volunteers given high inspired concentrations of sevoflurane (6 to 7%).

Methods: Twenty healthy persons who were 19 to 32 years old participated three times, received 6 l/min fresh gas flow, and were randomized to receive 6 to 7% sevoflurane in 66% nitrous oxide/28% oxygen by face mask until tracheal intubation (treatment 1) or until laryngeal mask airway insertion (treatment 3), or 6 to 7% sevoflurane without nitrous oxide to tracheal intubation (treatment 2). Participants exhaled to residual volume and took three vital capacity breaths of the gas mixture; thereafter ventilation was manually assisted. The time of exposure to the inhaled gas was varied for consecutive participants. It was either increased or decreased by 30-sec increments based on the failure or success of the preceding volunteer's response to laryngoscopy and intubation after a preselected exposure time. Failure was defined as poor jaw relaxation, coughing or bucking, or inadequate vocal cord relaxation.

Results: Loss of the lid-lash reflex in unpremedicated young volunteers was achieved in 1 min and did not differ among groups. Average time (and 95% confidence interval) for acceptable conditions for LMA insertion was achieved in 1.7 (0.7 to 2.7) min, and all participants had an immediate return of spontaneous ventilation. The time for acceptable tracheal intubating conditions after manual hyperventilation by mask was 4.7 (3.7 to 5.7) min and 6.4 (5.1 to 7.7) min in treatments 1 and 2, respectively. There were no cases of increased secretions or laryngospasm. The incidence of breath holding and expiratory stridor ("crowing") was 7.5% and 25%, respectively, during treatment 1 and 15% and 40%, respectively, during treatment 2.     

Epileptiform Electroencephalogram during Mask Induction of Anesthesia with Sevoflurane

Background: Sevoflurane is suggested as a suitable anesthetic agent for mask induction in adults. The authors recently found that hyperventilation during sevoflurane-nitrous oxide-oxygen mask induction is associated with cardiovascular hyperdynamic response. We tested the hypothesis that the hyperdynamic response can be explained by electroencephalography (EEG) findings.

Methods: Thirty women were randomly allocated to receive sevoflurane-nitrous oxygen-oxygen mask induction using a single-breath method, followed by either spontaneous breathing (n = 15) or controlled hyperventilation (n = 15) for 6 min. EEG was recorded. Blood pressure and heart rate were recorded at 1-min intervals.

Results: Epileptiform EEG activity (spikes or polyspikes) was seen in all patients with controlled hyperventilation, and in seven patients with spontaneous breathing (P< 0.01). Jerking movements were seen in three patients with controlled hyperventilation. In the controlled hyperventilation group, heart rate increased 54% from baseline at 4 min after induction (P< 0.001). Mean arterial pressure increased 17% (P< 0.05), peaking at 3 min. In the spontaneous breathing group, heart rate showed no change, and mean arterial pressure decreased by 14% (P< 0.01) at 6 min. Heart rate and mean arterial pressure differed significantly between the groups from 2 min after beginning of the induction to the end of the trial. An increase in heart rate of more than 30% from baseline always was associated with epileptiform EEG activity.     

Recovery Profile, Costs, and Patient Satisfaction with Propofol and Sevoflurane for Fast-track Office-based Anesthesia

Background: Office-based surgery is becoming increasingly popular because of its cost-saving potential. Both propofol and sevoflurane are commonly used in the ambulatory setting because of their favorable recovery profiles. This clinical investigation was designed to compare the clinical effects, recovery characteristics, and cost-effectiveness of propofol and sevoflurane when used alone or in combination for office-based anesthesia.

Methods: One hundred four outpatients undergoing superficial surgical procedures at an office-based surgical center were randomly assigned to one of three general anesthetic groups. In groups I and II, propofol 2 mg/kg was administered for induction followed by propofol 75-150 [micro sign]g [middle dot] kg-1 [middle dot] min-1 (group I) or sevoflurane 1-2% (group II) with N2 O 67% in oxygen for maintenance of anesthesia. In group III, anesthesia was induced and maintained with sevoflurane in combination with N (2) O 67% in oxygen. Local anesthetics were injected at the incision site before skin incision and during the surgical procedure. The recovery profiles, costs of drugs, and resources used, as well as patient satisfaction, were compared among the three treatment groups.

Results: Although early recovery variables (e.g., eye opening, response to commands, and sitting up) were similar in all three groups, the times to standing up and to be "home ready" were significantly prolonged when sevoflurane-N2 O was used for both induction and maintenance of anesthesia. The time to tolerating fluids, recovery room stay, and discharge times were significantly decreased when propofol was used for both induction and maintenance of anesthesia. Similarly, the incidence of postoperative nausea and vomiting and the need for rescue antiemetics were also significantly reduced after propofol anesthesia. Finally, the total costs and patient satisfaction were more favorable when propofol was used for induction and maintenance of office-based anesthesia.     

芬太尼对七氟醚麻醉诱导的影响

研究了２０例择期手术病人单吸七氟醚或七氟醚复合静注芬太尼麻醉诱导对呼吸、循环，量化脑电，肌 电活动及插管反应的影响。结论静注芬太尼复合七氟醚吸入明显协同诱导效率，在临床上优于单吸七氟醚诱导。     

Risk Factors for the Occurrence of Electroencephalogram Abnormalities during Induction of Anesthesia with Sevoflurane in Nonepileptic Patients

Background: The aim of this prospective study was to determine the risk factors of epileptiform discharge during induction with sevoflurane in healthy adult patients.

Methods: Forty adult patients with American Society of Anesthesiologists physical status I were randomly allocated to one of four groups. Group A: Patients breathed 8% sevoflurane in oxygen (8 l/min) via a prefilled circuit. End-tidal sevoflurane was maintained at 4%. Tracheal intubation was performed at the third minute after cisatracurium injection. Group B: The anesthesia protocol was similar, but a vital capacity technique was performed. Group C: Patients were anesthetized as in group A but were hyperventilated. Group D: Patients were anesthetized as in group A, but end-tidal sevoflurane was maintained at 2%. An electroencephalogram was recorded before and during induction up to 11 min after the start of induction. Statistical analysis was performed with Statview 5.0(R) (SAS Institute Inc., Cary, NC) for multivariate analysis.

Results: Twelve patients experienced epileptiform discharges. Risk factors were female sex (odds ratio, 12.60; 95% confidence interval, 1.46-135), delay to the occurrence of [beta] waves (odds ratio, 0.92; 95% confidence interval, 0.86-0.99), and end-tidal sevoflurane (odds ratio, 8.78; 95% confidence interval, 1.12-69). Epileptiform discharges were not associated with significant hemodynamic or Bispectral Index variations.     

Effects of Low-flow Sevoflurane Anesthesia on Renal Function: Comparison with High-flow Sevoflurane Anesthesia and Low-flow Isoflurane Anesthesia

Background: The safety of low-flow sevoflurane anesthesia, during which CF2 = C(CF3)-O-CH2 F (compound A) is formed by sevoflurane degradation, in humans has been questioned because compound A is nephrotoxic in rats. Several reports have evaluated renal function after closed-circuit or low-flow sevoflurane anesthesia, using blood urea nitrogen (BUN) and serum creatinine as markers. However, these are not the more sensitive tests for detecting renal damage. This study assessed the effects of low-flow sevoflurane anesthesia on renal function using not only BUN and serum creatinine but also creatinine clearance and urinary excretion of kidney-specific enzymes, and it compared these values with those obtained in high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia.

Methods: Forty-eight patients with gastric cancer undergoing gastrectomy were studied. Patients were randomized to receive sevoflurane anesthesia with fresh gas flow of 1 l/min (low-flow sevoflurane group; n = 16) or 6-10 l/min (high-flow sevoflurane group; n = 16) or isoflurane anesthesia with a fresh gas flow of 1 l/min (low-flow isoflurane group; n = 16). In all groups, the carrier gas was oxygen/nitrous oxide in the ratio adjusted to ensure a fractional concentration of oxygen in inspired gas (FiO2) of more than 0.3. Fresh Baralyme was used in the low-flow sevoflurane and low-flow isoflurane groups. Glass balls were used instead in the high-flow sevoflurane group, with the fresh gas flow rate adjusted to eliminate rebreathing. The compound A concentration was measured by gas chromatography. Gas samples taken from the inspiratory limb of the circle system at 1-h intervals were analyzed. Blood samples were obtained before and on days 1, 2, and 3 after anesthesia to measure BUN and serum creatinine. Twenty-four-hour urine samples were collected before anesthesia and for each 24-h period from 0 to 72 h after anesthesia to measure creatinine, N-acetyl-beta-D-glucosaminidase, and alanine aminopeptidase.

Results: The average inspired concentration of compound A was 20 +/- 7.8 ppm (mean +/- SD), and the average duration of exposure to this concentration was 6.11 +/- 1.77 h in the low-flow sevoflurane group. Postanesthesia BUN and serum creatinine concentrations decreased, creatinine clearance increased, and urinary N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase excretion increased in all groups compared with preanesthesia values, but there were no significant differences between the low-flow sevoflurane, high-flow sevoflurane, and low-flow isoflurane groups for any renal function parameter at any time after anesthesia.     

Changes in Electroencephalogram and Autonomic Cardiovascular Activity during Induction of Anesthesia with Sevoflurane Compared with Halothane in Children

Background: This study was design to assess clinical agitation, electroencephalogram (EEG) and autonomic cardiovascular activity changes in children during induction of anesthesia with sevoflurane compared with halothane using noninvasive recording of EEG, heart rate, and finger blood pressure.

Methods: Children aged 2-12 yr premedicated with midazolam were randomly assigned to one of three induction techniques: 7% sevoflurane in 100% O2 (group SevoRAPID); 2%, 4%, 6%, and 7% sevoflurane in 100% O2 (group SevoINCR); or 1%, 2%, 3%, and 3.5% halothane in 50% N2O-50% O2 (group HaloN2O). An additional group of children who received 7% sevoflurane in 50% N2O-50% O2 (group SevoN2O) was enrolled after completion of the study. Induction was videotaped. EEG, heart rate, and finger blood pressure were continuously recorded during induction until 5 min after tracheal intubation and analyzed in frequency domain using spectral analysis.

Results: Agitation was more frequent when anesthesia was induced with 100% O2 compared to the mixture of oxygen and nitrous oxide. No seizures were recorded in any group. In the four groups, induction of anesthesia was associated with an increase in EEG total spectral power and a shift toward the low-frequency bands. Sharp slow waves were present on EEG tracings of the three sevoflurane groups, whereas slow waves and fast rhythms (spindles) were observed in the halothane group. Sevoflurane induced a greater withdrawal of parasympathetic activity than halothane and a transient relative increase in sympathetic vascular tone at loss of eyelash reflex.     

A Single Dose of Propofol at the End of Surgery for the Prevention of Emergence Agitation in Children Undergoing Strabismus Surgery during Sevoflurane Anesthesia

Background: Emergence agitation in children after sevoflurane is common. Different drugs have been used to decrease its occurrence with variable efficacy. The authors compared the incidence and severity of emergence agitation in children who received a single dose of propofol at the end of strabismus surgery versus children who received saline.

Methods: In this prospective, randomized, double-blind study, the authors enrolled 80 healthy children aged 2-6 yr. The children were randomly allocated to the propofol group (n = 41), which received 1 mg/kg propofol at the end of surgery, or to the saline group (n = 39), which received saline.

Results: The mean scores on the Pediatric Anesthesia Emergence Delirium scale were significantly lower in the propofol group compared with the saline group (8.6 +/- 3.9 vs. 11.5 +/- 4.5; P = 0.004). Also, the incidence of agitation was significantly lower in the propofol group compared with the saline group (19.5% vs. 47.2%; P = 0.01). A threshold score greater than 10 on the Pediatric Anesthesia Emergence Delirium scale was the best discriminator between presence and absence of emergence agitation. Times to removal of the laryngeal mask airway (10.6 +/- 1.5 vs. 9.4 +/- 1.9 min; P = 0.004) and emergence times (23.4 +/- 5.7 vs. 19.7 +/- 5 min; P = 0.004) were significantly longer in the propofol group. However, discharge times were similar between the two groups (propofol: 34.1 +/- 8.4 min; saline: 34.9 +/- 8.6 min). More parents in the propofol group were satisfied.     

Effects of A-Line Autoregression Index (AAI) Monitoring on Recovery After Sevoflurane Anesthesia for Bariatric Surgery

Monitoring depth of anesthesia may improve anesthetic dosing and postanesthetic recovery in obese patients. Sixty morbidly obese patients undergoing laparoscopic adjustable gastric bandage (LAGB) were randomly assigned to receive anesthesia with sevoflurane titrated by either standard clinical parameters (SCP) (target = baseline hemodynamic parameters ± 20%) or by A-line ARX index (AAI) (target = 20 ± 5). Heart rate, arterial blood pressure, inspiratory and expiratory gas concentrations, and AAI were recorded in all patients at 5-min intervals, but AAI was made available only to the anesthesiologist assigned to AAI-monitored patients. Emergence times in surgery room and recovery times in postanesthesia care unit (PACU) were recorded at 1- and 30-min intervals. Mean intraoperative values of AAI were higher in AAI-monitored than in SCP-monitored patients (22.5 vs 15.0, p = 0.001). Compared to SCP monitoring, AAI monitoring reduced consumption of sevoflurane by 20% (p = 0.014), times to eye opening by 2.4 min (p = 0.001) and to extubation by 2.5 min (p = 0.009) and to achieve SpO₂ 92% in room air by 17 min (p = 0.001). Aldrete scores were higher in AAI- than in SCP-monitored patients at arrival in PACU (p = 0.035), but Aldrete scores ≥9 were attained in similar times. AAI monitoring can improve titration of and recovery from sevoflurane for LAGB.     

Does the Use of Electroencephalographic Bispectral Index or Auditory Evoked Potential Index Monitoring Facilitate Recovery after Desflurane Anesthesia in the Ambulatory Setting?

Background: Analogous to the Bispectral Index(R) (BIS(R)) monitor, the auditory evoked potential monitor provides an electroencephalographic-derived index (AAI), which is alleged to correlate with the central nervous system depressant effects of anesthetic drugs. This clinical study was designed to test the hypothesis that intraoperative cerebral monitoring guided by either the BIS or the AAI value would facilitate recovery from general anesthesia compared with standard clinical monitoring practices alone in the ambulatory setting.

Methods: Sixty consenting outpatients undergoing gynecologic laparoscopic surgery were randomly assigned to one of three study groups: (1) control (standard practice), (2) BIS guided, or (3) AAI guided. Anesthesia was induced with 1.5-2.5 mg/kg propofol and 1-1.5 [mu]g/kg fentanyl given intravenously. Desflurane, 3%, in combination with 60% nitrous oxide in oxygen was administered for maintenance of general anesthesia. In the control group, the inspired desflurane concentration was varied based on standard clinical signs. In the BIS- and AAI-guided groups, the inspired desflurane concentrations were titrated to maintain BIS and AAI values in targeted ranges of 50-60 and 15-25, respectively. BIS and AAI values, hemodynamic variables, and the end-tidal desflurane concentration were recorded at 5-min intervals during the maintenance period. The emergence times and recovery times to achieve specific clinical endpoints were recorded at 1- to 10-min intervals. The White fast-track and modified Aldrete recovery scores were assessed on arrival in the PACU, and the quality of recovery score was evaluated at the time of discharge home.

Results: A positive correlation was found between the AAI and BIS values during the maintenance period. The average BIS and AAI values (mean +/- SD) during the maintenance period were significantly lower in the control group (BIS, 41 +/- 10; AAI, 11 +/- 6) compared with the BIS-guided (BIS, 57 +/- 14; AAI, 18 +/- 11) and AAI-guided (BIS, 55 +/- 12; AAI, 20 +/- 10) groups. The end-tidal desflurane concentration was significantly reduced in the BIS-guided (2.7 +/- 0.9%) and AAI-guided (2.6 +/- 0.9%) groups compared with the control group (3.6 +/- 1.5%). The awakening (eye-opening) and discharge times were significantly shorter in the BIS-guided (7 +/- 3 and 132 +/- 39 min, respectively) and AAI-guided (6 +/- 2 and 128 +/- 39 min, respectively) groups compared with the control group (9 +/- 4 and 195 +/- 57 min, respectively). More importantly, the median [range] quality of recovery scores was significantly higher in the BIS-guided (18 [17-18]) and AAI-guided (18 [17-18]) groups when compared with the control group (16 [10-18]).     

Use of Intranasal Fentanyl in Children Undergoing Myringotomy and Tube Placement during Halothane and Sevoflurane Anesthesia

Background: Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia.

Methods: In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 [mu]g/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 [mu]g/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated.

Results: In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl.     

地氟醚、七氟醚与安氟醚低流量麻醉临床观察

比较地氟醚、七氟醚、安氟醚用于低流麻醉时ＢＰ和ＨＲ改变,苏醒过程、不良反应以及药物费用。方法：４２例ＡＳＡＩⅠ－Ⅱ级择期腹部外科手术病人随机分成地氟醚,安氟醚和七氟醚三组。麻醉诱导后连接Ｃｉｃｅｒｏ麻醉机。降低新鲜气流,地氟醚和安氟醚为０．３－０．５Ｌ／ｍｉｎ,七氟醚为０．８－１．０Ｌ／ｍｉｎ,从回路呼出端向麻醉机回路内注入液吸入麻醉药４－５分钟内使三组病人呼气末麻醉药浓度达到１ＭＡＣ左右,即地氟     

Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting

The present guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in postoperative nausea and vomiting (PONV) under the auspices of The Society of Ambulatory Anesthesia. The panel critically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. In brief, these guidelines identify risk factors for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic monotherapy and combination therapy regimens for PONV prophylaxis; recommend approaches for treatment of PONV when it occurs; and provide an algorithm for the management of individuals at increased risk for PONV.     

Evaluation of the Alaris Auditory Evoked Potential Index as an Indicator of Anesthetic Depth in Preschool Children during Induction of Anesthesia with Sevoflurane and Remifentanil

Background: Autoregressive modeling with exogenous input of middle latency auditory evoked potentials (A-Line autoregressive index [AAI]) has been proposed for monitoring depth of anesthesia in adults. The aim of this study was to evaluate the performance of the AAI during induction of anesthesia with sevoflurane and remifentanil in pediatric patients.

Methods: Twenty preschool children were anesthetized with sevoflurane and remifentanil. AAI, heart rate, and mean arterial pressure were compared for their ability to distinguish between different hypnotic states before inhalation induction and during sevoflurane anesthesia with and without remifentanil infusion. The prediction probability was calculated for discrimination between the predefined case milestones Awake, Spontaneous Eye Closure, and insertion of a laryngeal mask airway during general anesthesia (Laryngeal Mask Insertion).

Results: The AAI (mean +/- SD) in Awake children was 79 +/- 10, declining to 59 +/- 22 at Spontaneous Eye Closure and 34 +/- 13 when anesthetized. AAI values significantly overlapped between anesthetic states. For the AAI, the prediction probabilities regarding the ability to discriminate the hypnotic state at the case milestones Awake versus Spontaneous Eye Closure and Awake versus Laryngeal Mask Insertion were 0.77 and 0.99, respectively. In terms of prediction probability values, heart rate and mean arterial pressure were not indicative for anesthetic states. Remifentanil did not influence the AAI.