The Effect of Fentanyl on Sevoflurane Requirements for Somatic and Sympathetic Responses to Surgical Incision

Background: Fentanyl produces a reduction in the minimum alveolar concentration (MAC) of isoflurane and desflurane needed to blockade adrenergic response (BAR) to surgical incision in 50% of patients (MAC-BAR). MAC-BAR of sevoflurane and the reduction in MAC-BAR of sevoflurane by fentanyl have not been described previously. The purpose of this study was to determine the MAC and MAC-BAR reduction of sevoflurane by fentanyl with and without nitrous oxide (N2 O).

Methods: Two hundred twenty-six patients were randomly assigned to one of two groups: a sevoflurane group and a sevoflurane/N2 O group. Patients in each group were randomly assigned to one of five different fentanyl concentration subgroups. Patients were anesthetized with sevoflurane and fentanyl in the sevoflurane group and with sevoflurane, fentanyl, and N (2) O (66 vol%) in the sevoflurane/N2 O group. Somatic and sympathetic responses to surgical incision were observed for MAC and MAC-BAR assessment at predetermined concentrations of sevoflurane.

Results: Fentanyl produced an initial steep reduction in the MAC and MAC-BAR of sevoflurane, with 3 ng/ml resulting in a 61% reduction in MAC and an 83% reduction in MAC-BAR. A ceiling effect was observed for MAC and MAC-BAR, with 6 ng/ml fentanyl providing only an additional 13% and 9% reduction in MAC and MAC-BAR, respectively. In the presence of 66 vol% N2 O, MAC and MAC-BAR of sevoflurane were reduced with increasing concentrations of fentanyl. A ceiling effect was not observed for reduction in MAC and MAC-BAR in the presence of N2 O.     

Anesthetic Doses of Sevoflurane To Block Cardiovascular Responses to Incision when Administered with Xenon or Nitrous Oxide

Background: The authors' previous study demonstrated that xenon (Xe) and nitrous oxide (N2 O) in combination with sevoflurane can attenuate cardiovascular responses to skin incision. To quantitatively evaluate their suppressive effects on cardiovascular responses, the authors compared the MAC-BAR (minimum alveolar concentration that blocks adrenergic or cardiovascular response to incision) values of sevoflurane when administered with Xe or N2 O.

Methods: Forty-three patients received sevoflurane with one of three anesthetics; 1 MAC Xe, 0.7 MAC Xe and 0.7 MAC N2 O. The MAC-BAR of sevoflurane was determined in each anesthetic using the "up and down" method. The response was considered positive if the heart rate or mean arterial pressure increased 15% or more. The end-tidal sevoflurane concentration given to the next patient was increased or decreased by 0.3 MAC if the response was positive or negative in the previous patient, respectively. The MAC-BAR was calculated as the mean of four independent cross-over responses.

Results: The MAC-BAR of sevoflurane, including the contribution of Xe or N2 O, was 2.1 +/- 0.2 MAC and 2.7 +/- 0.2 MAC when administered with 1 MAC Xe, respectively, and 2.6 +/- 0.4 MAC when administered with 0.7 MAC N (2) O (mean +/- SD).     

Plasma Concentration of Fentanyl with Xenon to Block Somatic and Hemodynamic Responses to Surgical Incision

Background: Although anesthesia with xenon has been supplemented with fentanyl, its requirement has not been established. This study was conducted to determine the plasma concentrations of fentanyl necessary to suppress somatic and hemodynamic responses to surgical incision in 50% patients in the presence of 0.7 minimum alveolar concentration (MAC) xenon.

Methods: Twenty-five patients were allocated randomly to predetermined fentanyl concentration between 0.5 and 4.0 ng/ml during 0.7 MAC xenon anesthesia. Fentanyl was administered using a pharmacokinetic model-driven computer-assisted continuous infusion device. At surgical incision each patient was monitored for somatic and hemodynamic responses. A somatic response was defined as any purposeful bodily movement. A positive hemodynamic response was defined as a more than 15% increase in heart rate or mean arterial pressure more than the preincision value. The concentrations of fentanyl to prevent somatic and hemodynamic responses in 50% of patients were calculated using logistic regression.

Results: The concentration of fentanyl to prevent a somatic response to skin incision in 50% of patients in the presence of 0.7 MAC xenon was 0.72 +/- 0.07 ng/ml and to prevent a hemodynamic response was 0.94 +/- 0.06 ng/ml.     

The Effects of Fentanyl on Sevoflurane Requirements for Loss of Consciousness and Skin Incision

Background: Fentanyl produces a minimal reduction in the minimum alveolar concentration of sevoflurane to prevent response to a verbal command in 50% of patients (MACawake) at low but analgesic plasma concentrations. The reduction in MACawake, however, is still unknown at higher fentanyl concentrations. The reduction in the MAC of sevoflurane by fentanyl has not been described accurately. The purpose of this study was to determine the MACawake and MAC reduction of sevoflurane by fentanyl.

Methods: Ninety-two patients were randomly allocated to seven fentanyl concentration groups (target plasma concentrations of 0, 1, 1.5, 3, 6, 10, and 14 ng/ml). Responses to verbal command were observed for MACawake assessment at predetermined sevoflurane concentrations. Thereafter, in patients whose target fentanyl concentration was 0 to 10 ng/ml, responses to skin incision were observed for MAC assessment at new steady-state sevoflurane concentrations. The reduction in the MACawake and MAC of sevoflurane by the measured fentanyl concentration was calculated.

Results: There was an initial steep reduction in the MAC of sevoflurane by fentanyl, with 3 ng/ml resulting in a 59% MAC reduction. A ceiling effect was observed, with 10 ng/ml providing only a further 17% reduction in MAC. The initial reduction in MACawake was not as steep as that in MAC. Fentanyl reduced MACawake by approximately 24% at a plasma concentration of 3 ng/ml. Although the reduction curve of MACawake was parabolic, no manifest ceiling effect was observed at concentrations administered in the present study.     

Interaction of Propofol and Sevoflurane on Loss of Consciousness and Movement to Skin Incision during General Anesthesia

Background: Loss of consciousness (LOC) and immobility to surgical incision seem to be mediated at different levels of the central nervous system. Pharmacologic studies of hypnotic agents have previously focused on combinations of either volatile or intravenous anesthetics. This study examined the combination of inhaled sevoflurane and intravenous propofol at these two clinically relevant anesthetic end points.

Methods: Thirty-six elective surgical patients were initially enrolled. Conditions approximating steady state were obtained for sevoflurane and target-controlled propofol infusions. Patients were sequentially evaluated for LOC (loud voice plus mild prodding) and immobility to surgical incision. The study was designed using the Dixon up-down method.

Results: The observed propofol effect target with 50% response plus sevoflurane (0.46% end-tidal concentration) was 1.2 [mu]g/ml (95% confidence interval, 1.1-1.3 [mu]g/ml). It was not significantly different from that predicted (1.5 [mu]g/ml; 95% confidence interval, 1.2-1.7 [mu]g/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 [mu]g/ml (95% confidence interval, 4.8-6.0 [mu]g/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 [mu]g/ml; 95% confidence interval, 4.8-5.9 [mu]g/ml). Both analyses had adequate power (90%) to detect a significant change (+/-19 to 25%) from predicted value. Repeated-measures analysis of variance identified a Bispectral Index value of 70 as the break point between those who responded at LOC or did not.     

Auditory Evoked Potential Index Predicts the Depth of Sedation and Movement in Response to Skin Incision during Sevoflurane Anesthesia

Background: The auditory evoked potential (AEP) index, which is a single numerical parameter derived from the AEP in real time and which describes the underlying morphology of the AEP, has been studied as a monitor of anesthetic depth. The current study was designed to evaluate the accuracy of AEPindex for predicting depth of sedation and anesthesia during sevoflurane anesthesia.

Methods: In the first phase of the study, a single end-tidal sevoflurane concentration ranging from 0.5 to 0.9% was assigned randomly and administered to each of 50 patients. The AEPindex and the Bispectral Index (BIS) were obtained simultaneously. Sedation was assessed using the responsiveness portion of the observer's assessment of alertness-sedation scale. In the second phase of the study, 10 additional patients were included, and the 60 patients who were scheduled to have skin incisions were observed for movement in response to skin incision at the end-tidal sevoflurane concentrations between 1.6 and 2.6%. The relation among AEPindex, BIS, sevoflurane concentration, sedation score, and movement or absence of movement after skin incision was determined. Prediction probability values for AEPindex, BIS, and sevoflurane concentration to predict depth of sedation and anesthesia were also calculated.

Results: The AEPindex, BIS, and sevoflurane concentration correlated closely with the sedation score. The prediction probability values for AEPindex, BIS, and sevoflurane concentration for sedation score were 0.820, 0.805, and 0.870, respectively, indicating a high predictive performance for depth of sedation. AEPindex and sevoflurane concentration successfully predicted movement after skin (prediction probability = 0.910 and 0.857, respectively), whereas BIS could not (prediction probability = 0.537).     

Effects of Xenon on Hemodynamic Responses to Skin Incision in Humans

Background: The authors evaluated the hemodynamic suppressive effects of xenon in combination with sevoflurane at skin incision in patients undergoing surgery.

Methods: Forty patients were assigned randomly to receive one of the following four anesthetics: 1.3 minimum alveolar concentration (MAC) sevoflurane, 0.7 MAC xenon with 0.6 MAC sevoflurane, 1 MAC xenon with 0.3 MAC sevoflurane, or 0.7 MAC nitrous oxide with 0.6 MAC sevoflurane (n = 10 each group). Systolic blood pressure and heart rate were measured before anesthesia, before incision, and approximately 1 min after incision.

Results: The changes in hemodynamic variables in response to incision were less with sevoflurane in combination with xenon and nitrous oxide than with sevoflurane alone. Changes in heart rate (in beats/min) were 19 +/- 11 (+/- SD) for sevoflurane alone, 11 +/- 6 for 0.7 MAC xenon-sevoflurane, 4 +/- 4 for 1 MAC xenon-sevoflurane, and 8 +/- 7 for nitrous oxide-sevoflurane. Changes in systolic blood pressure were 35 +/- 18 mmHg for sevoflurane alone, 18 +/- 8 mmHg for 0.7 MAC xenon-sevoflurane, 16 +/- 7 mmHg for 1 MAC xenon-sevoflurane, and 14 +/- 10 mmHg for nitrous oxide-sevoflurane.     

The Pharmacodynamic Interaction between Propofol and Fentanyl with Respect to the Suppression of Somatic or Hemodynamic Responses to Skin Incision, Peritoneum Incision, and Abdominal Wall Retraction

Background: Sufficient propofol or fentanyl doses necessary to prevent the response to skin incision do not necessarily attenuate hemodynamic responses during surgery. The goal of this study was to characterize the pharmacodynamic interaction between propofol and fentanyl with respect to the suppression of somatic or hemodynamic responses after three stimuli: skin incision, peritoneum incision, and abdominal wall retraction.

Methods: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide equilibration between plasma-blood and biophase concentrations. Patients were randomized to nine groups that received predetermined concentrations of fentanyl (from 0 to 9 ng/ml). Each patient was administered different target concentrations of propofol. Somatic and hemodynamic responses were measured before and after each of three different stimulations: skin incision (si), peritoneum incision (pi), and abdominal wall retraction (ret). The propofol plasma concentrations at which 50% of the patients did not respond to each type of stimulation (Cp50si, Cp50pi, and Cp50ret) were calculated by fitting the Loewe synergistic model.

Results: For propofol alone, Cp50si, Cp50pi, and Cp50ret were 12.9, 17.1 and 19.4 [micro sign]g/ml, respectively. Increasing the fentanyl concentration markedly reduced propofol Cp50si, Cp50pi, and Cp50ret for somatic response, indicating the potential synergistic interaction of both drugs. During the prestimulation period, fentanyl did not decrease systolic blood pressure; however, propofol specifically decreased systolic blood pressure. Both drugs had a synergistic drug interaction on the systolic blood pressure increase after various surgical stimulations. Fentanyl and propofol concentrations that suppressed both the 50% probability of somatic response and the 50% probability of moderate hemodynamic change defined by the 15% systolic blood pressure increase over the prestimulation value were 3.6 ng/ml and 2.5 [micro sign]g/ml for skin incision, 8.4 ng/ml and 1.6 [micro sign]g/ml for peritoneum incision, and 5.9 ng/ml and 5.1 [micro sign]g/ml for wall retraction, respectively.     

腹腔镜手术全身麻醉中联合应用瑞芬太尼与七氟烷药效学相互作用的研究

目的探讨腹腔镜手术全身麻醉中瑞芬太尼与七氟烷的药效学相互作用。方法ASAⅠ级妇科或外科拟行择期腹腔镜手术的患者65例,每名患者预先选定七氟烷的目标浓度,并在试验过程中维持七氟烷呼出浓度恒定。采用七氟烷吸入诱导。当呼气末七氟烷浓度达到设定浓度,观察七氟烷与瑞芬太尼不同剂量组合(0、1、2、4、6和8ng/ml)时,患者对100Hz、60mA、5s的强直电刺激(electrical tetanus stimuli,ETS)的体动和循环反应。应用NONMEM软件对原始数据进行分析和浓度-效应曲线(即S形曲线)的拟合。Logistic回归模型求算七氟烷强直电刺激时的肺泡最低有效浓度(minimal alveolar concentration,MAC)。结果单独应用七氟烷,抑制ETS引起体动反应的MACETS为1.52%,抑制ETS引起循环反应的MACETS为2.24%。小剂量的瑞芬太尼即可明显降低七氟烷的MACETS。当瑞芬太尼的靶控浓度为8ng/ml时,抑制强直电刺激体动反应和循环反应的MACETS值分别下降70.0%和76.3%。结论瑞芬太尼与七氟烷在抑制强直电刺激的体动和循环反应方面存在协同作用。瑞芬太尼可以...     

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.     

Compound A Concentrations during Sevoflurane Anesthesia in Children

Background: Sevoflurane is a new inhalation agent that should be useful for pediatric anesthesia. Sevoflurane undergoes degradation in the presence of carbon dioxide absorbents; however, quantification of the major degradation product (compound A) has not been evaluated during pediatric anesthesia. This study evaluates sevoflurane degradation compound concentrations during sevoflurane anesthesia using a 2-1 fresh gas flow and a circle system with carbon dioxide absorber in children with normal renal and hepatic function.

Methods: The concentrations of compound A were evaluated during sevoflurane anesthesia in children using fresh soda lime as the carbon dioxide absorbent. Nineteen patients aged 3 months-7 yr were anesthetized with sevoflurane (2.8% mean end-tidal concentration) using a total fresh gas flow of 2 l in a circle absorption system. Inspiratory and expiratory limb circuit gas samples were obtained at hourly intervals, and the samples were analyzed using a gas chromatography-flame ionization detection technique. Carbon dioxide absorbent temperatures were measured in the soda lime during anesthesia. Blood samples were obtained before and after anesthesia for hepatic and renal function studies. Venous blood samples were obtained before anesthesia, at the end of anesthesia, and 2 h after anesthesia for plasma inorganic fluoride ion concentration.

Results: The maximum inspiratory concentration of compound A was 5.4 +/-4.4 ppm (mean+/-SD), and the corresponding expiratory concentration was 3.7+/-2.7 ppm (mean+/-SD). The maximum inspiratory compound A concentration in any patient was 15 ppm. Mean concentrations of compound A peaked at intubation and remained stable, declining slightly after 120 min of anesthesia. The duration of anesthesia was 240+/-139 min (mean+/-SD). Maximum soda lime temperature ranged between 23.1 degrees C and 40.9 degrees C. There was a positive correlation between maximum absorbent temperature and maximum compound A concentration (r2 = 0.58), as well as between the child's body surface area and maximum compound A concentration (r2 = 0.59). Peak plasma inorganic fluoride ion concentration was 21.5 +/-6.1 micro mol/l. There were no clinically significant changes in hepatic or renal function studies performed 24 h postanesthesia.     

Effects of Propofol and Remifentanil on Phrenic Nerve Activity and Nociceptive Cardiovascular Responses in Rabbits

Background: The effects of propofol, remifentanil, and their combination on phrenic nerve activity (PNA), resting heart rate (HR), mean arterial pressure (MAP), and nociceptive cardiovascular responses were studied in rabbits.

Methods: Basal anesthesia and constant blood gas tensions were maintained with [alpha]-chloralose and mechanical ventilation. PNA, HR, MAP, and maximum changes in HR and MAP ([DELTA]HR, [DELTA]MAP) evoked by electrical nerve stimulation of tibial nerves were recorded. The comparative effects were observed for propofol at infusion rates from 0.05 to 3.2 mg [middle dot] kg-1 [middle dot] min-1 (group I) and remifentanil from 0.0125 to 12.8 [mu]g [middle dot] kg-1 [middle dot] min-1 alone (group II), and during constant infusions of propofol at rates of 0.1 and 0.8 mg [middle dot] kg-1 [middle dot] min-1 (groups III and IV, respectively). Finally, the effect of remifentanil on propofol blood levels was observed (group V).

Results: The infusion rates for 50% depression (ED50) of PNA, [DELTA]HR, and [DELTA]MAP were 0.41, 1.32, and 1.58 mg [middle dot] kg-1 [middle dot] min-1 for propofol, and 0.115, 0.125, and 1.090 [mu]g [middle dot] kg-1 [middle dot] min-1 for remifentanil, respectively. The ratios for the ED50 values of [DELTA]HR and [DELTA]MAP to PNA were 3.2 and 3.9 for propofol, and 1.1 and 9.5 for remifentanil, respectively. Analysis of the expected and observed responses and isobologrms showed that although their combined effects on PNA, resting HR, and MAP, and [DELTA]MAP were synergistic for [DELTA]HR, they were merely additive. Remifentanil had no effect on propofol blood levels.     

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.     

Residual Block after Mivacurium with or without Edrophonium Reversal in Adults and Children

Background: The rapid recovery from mivacurium-induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit.

Methods: In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg *symbol* kg sup -1 edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode.

Results: Children arrived in the postanesthesia care unit 8.2 +/-3.4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/-0.05 vs. 0.93+/-0.01, P < 0.01), TOF was > 0.7 in all children. Adults arrived in the postanesthesia care unit 12.9+/- 5.3 min after reversal of neuromuscular block (P < 0.01 vs. children). Six in the saline group demonstrated weakness (two required immediate reversal of neuromuscular block, and TOF was < 0.7 in four others), compared with TOF < 0.7 in only one of the edrophonium group (P < 0.05).     

Determination of the Pharmacodynamic Interaction of Propofol and Remifentanil during Esophagogastroduodenoscopy in Children

Background: Propofol is commonly used to anesthetize children undergoing esophagogastroduodenoscopy. Opioids are often used in combination with propofol to provide total intravenous anesthesia. Because both propofol and remifentanil are associated with rapid onset and offset, the combination of these two drugs may be particularly useful for procedures of short duration, including esophagogastroduodenoscopy. The authors previously demonstrated that the median effective concentration (C50) of propofol during esophagogastroduodenoscopy in children is 3.55 [mu]g/ml. The purpose of this study was to describe the pharmacodynamic interaction of remifentanil and propofol when used in combination for esophagogastroduodenoscopy in pediatric patients.

Methods: The authors studied 32 children aged between 3 and 10 yr who were scheduled to undergo esophagogastroduodenoscopy. Propofol was administered via a target-controlled infusion system using the STANPUMP software based on a pediatric pharmacokinetic model. Remifentanil was administered as a constant rate infusion of 25, 50, and 100 ng [middle dot] kg-1 [middle dot] min-1 to each of three study groups, respectively. A sigmoid Emax model was developed to describe the interaction of remifentanil and propofol.

Results: There was a positive interaction between remifentanil and propofol when used in combination. The concentration of propofol alone associated with 50% probability of no response was 3.7 [mu]g/ml (SE, 0.4 [mu]g/ml), and this was decreased to 2.8 [mu]g/ml (SE, 0.1 [mu]g/ml) when used in combination with remifentanil.     

Renal Responses to Low-flow Desflurane, Sevoflurane, and Propofol in Patients

Background: The contributing factors that result in significant, postoperative proteinuria and glucosuria after low-flow isoflurane and sevoflurane anesthesia are unknown. The present study compared renal responses after anesthesia with desflurane (negligible metabolism), sevoflurane, or intravenous propofol.

Methods: Informed consent was obtained from 52 patients with American Society of Anesthesiologists physical status I-III (aged 36-81 yr). Patients with diabetes or renal insufficiency were excluded. Desflurane (n = 20) or sevoflurane (n = 22), without nitrous oxide, was given at 1 l/min fresh gas flow for elective surgical procedures lasting more than 2 h; 10 patients received propofol without nitrous oxide as the primary anesthetic. Blood and urine chemistries were obtained before surgery. Blood and 24-h urine collections were obtained for 3 days after surgery and were analyzed for liver and renal indices.

Results: Length of surgery averaged ~ 300 min (range, 136-750 min), minimum alveolar concentration-hour averaged 4.3 (range, 1.2-11.0), and infusion rates of propofol were 99-168 [mu]g [middle dot] kg-1 [middle dot] min-1. Plasma creatinine concentration did not change, plasma blood urea nitrogen decreased significantly, and significant increases in urine glucose, protein, and albumin occurred similarly in all groups. Mean (+/- SD) postoperative urine glucose values for day 1 after desflurane, sevoflurane, and propofol were 1.4 +/- 3.0, 1.1 +/- 2.1, and 1.9 +/- 2.6 g/d (normal, < 0.5 g/d). The average daily protein/creatinine ratios for postoperative days 2-3 after desflurane, sevoflurane, and propofol were 240 +/- 187, 272 +/- 234, and 344 +/- 243 (normal,< 150 mg/g). Regardless of anesthetic, there were significantly greater urine protein concentrations after surgical procedures in central versus peripheral regions.     

Dose Responses for Neostigmine and Edrophonium as Antagonists of Mivacurium in Adults and Children

Background: Reversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults. The purpose of this study was to compare the spontaneous and neostigmine- and edrophonium-assisted recovery of mivacurium-induced neuromuscular block in adults and children.

Methods: Fifty-four adults, aged 40.1+/-10.9 yr, and 54 children, aged 4.9+/-0.7 yr, physical status ASA 1-2, were studied during propofol/fentanyl/nitrous oxide anesthesia. A Datex relaxograph was used to monitor the electromyographic response of the adductor pollicis to train-of-four stimulation of the ulnar nerve every 10 s. After induction of anesthesia, 0.2 mg *symbol* kg sup -1 intravenous mivacurium was administered followed by an infusion to maintain 90-95% T1 block. At the end of surgery, one of four doses of neostigmine (5, 10, 20, and 50 micro gram *symbol* kg sup -1) or edrophonium (100, 200, 400, and 1,000 micro gram *symbol* kg sup -1) or placebo was given, by random allocation, when T1 had recovered to 10%. Values of T1 and train-of-four were measured for 10 min.

Results: Spontaneous recovery proceeded more rapidly in children than in adults. At 10 min, T1 had recovered to 97+/-2% (SD) in children compared with 69+/-11% in adults and train-of-four to 84 +/-5% versus 30+/-13% (P < 0.0001). In children, 10 min after reversal, recovery of T1 and train-of-four was not different from control after edrophonium and was enhanced only by the larger doses of neostigmine. In adults, recovery was accelerated by both edrophonium and neostigmine. Five minutes after reversal, recovery was improved by either drug in adults and in children.     

Isoflurane and Sevoflurane Augment Norepinephrine Responses to Surgical Noxious Stimulation in Humans

Background: Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics.

Methods: Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values.

Results: Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase the area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations.     

Sevoflurane Concentrations Required to Block Autonomic Hyperreflexia during Transurethral Litholapaxy in Patients with Complete Spinal Cord Injury

Background: Autonomic hyperreflexia (AHR) is a potentially life-threatening hypertensive condition that occurs in patients with high spinal cord injury (SCI). The current study was aimed to determine sevoflurane concentrations that block AHR in SCI patients.

Methods: The study involved 28 patients with chronic, complete SCI scheduled to undergo transurethral litholapaxy during general anesthesia. Nine patients without SCI served as controls post hoc. Anesthesia was induced with thiopental, and sevoflurane concentrations in 50% nitrous oxide were adjusted to maintain a Bispectral Index of 40-50. When a patient developed AHR during bladder distension, the target sevoflurane concentration was maintained for at least 10 min, and then the procedure was resumed. Systolic blood pressure, heart rate, and Bispectral Index as well as plasma concentrations of catecholamines and arginine vasopressin were measured before and during the bladder distension. Each target concentration was determined by the up-and-down method based on changes (15% increase or more) of systolic blood pressure in response to bladder distension.

Results: In SCI, systolic pressure increased by 67 +/- 33 mmHg, whereas heart rate decreased by 13 +/- 8 beats/min during the first trial (P < 0.01). The hypertensive event was associated with increases of norepinephrine concentrations, but not of epinephrine or vasopressin concentrations. Systolic pressure, heart rate, and norepinephrine concentrations did not change significantly in the control patients. The end-tidal concentrations of sevoflurane to prevent AHR were EC50 of 3.12% and EC95 of 3.83%.