Dixon Up-down Method Research Articles

Electroencephalographic Indices for Clinical Endpoints during Propofol Anesthesia in Infants: An Early-phase Propofol Biomarker-finding Study.

Unlike expired sevoflurane concentration, propofol lacks a biomarker for its brain effect site concentration, leading to dosing imprecision particularly in infants. Electroencephalography monitoring can serve as a biomarker for propofol effect site concentration, yet proprietary electroencephalography indices are not validated in infants. The authors evaluated spectral edge frequency (SEF95) as a propofol anesthesia biomarker in infants. It was hypothesized that the SEF95 targets will vary for different clinical stimuli and an inverse relationship existed between SEF95 and propofol plasma concentration. This prospective study enrolled infants (3 to 12 months) to determine the SEF95 ranges for three clinical endpoints of anesthesia (consciousness-pacifier placement, pain-electrical nerve stimulation, and intubation-laryngoscopy) and correlation between SEF95 and propofol plasma concentration at steady state. Dixon's up-down method was used to determine target SEF95 for each clinical endpoint. Centered isotonic regression determined the dose-response function of SEF95 where 50% and 90% of infants (ED50 and ED90) did not respond to the clinical endpoint. Linear mixed-effect model determined the association of propofol plasma concentration and SEF95. Of 49 enrolled infants, 44 evaluable (90%) showed distinct SEF95 for endpoints: pacifier (ED50, 21.4 Hz; ED90, 19.3 Hz), electrical stimulation (ED50, 12.6 Hz; ED90, 10.4 Hz), and laryngoscopy (ED50, 8.5 Hz; ED90, 5.2 Hz). From propofol 0.5 to 6 μg/ml, a 1-Hz SEF95 increase was linearly correlated to a 0.24 (95% CI, 0.19 to 0.29; P < 0.001) μg/ml decrease in plasma propofol concentration (marginal R2 = 0.55). SEF95 can be a biomarker for propofol anesthesia depth in infants, potentially improving dosing accuracy and utilization of propofol anesthesia in this population.

Gabapentin regulates dopaminergic neuron firing and theta oscillation in the ventral tegmental area to reverse depression-like behavior in chronic neuropathic pain state.

PurposeVentral tegmental area (VTA) dopamine system plays an important role in depression and is also involved in pain experience. In this study, we investigated the VTA dopaminergic (DA) neuron firing and local field potential (LFP) in pain-related depression, and we try to explore the underlying relationship between pain and depression.Materials and methodsWe used neuropathic pain model [spare nerve injury (SNI)] to induce pain-related depression. The Dixon up–down method was used to test mechanical hypersensitivity. Behavioral changes like open field test, sucrose preference test, and forced swim test were used to test depression-like behaviors. Gabapentin (GBP) was used to explore the chronic analgesic treatment that could reverse pain-related depression. To investigate the in vivo variations of VTA DA neuron firing and LFP, multichannel acquisition processor system was used.ResultsWe used SNI to induce depression-like behaviors. Repeated GBP treatment reversed these behaviors after 14 days of injection. An in vivo electrophysiological analysis of the firing characteristics of VTA DA neurons and LFP revealed that SNI increased the firing rate of DA neurons, but not the burst firing activity. Surprisingly, chronic GBP reversed the firing rate of DA neurons and reduced the burst firing activity. Moreover, SNI increased the LFP power in delta and theta oscillation and decreased it in beta oscillation. Repeated administration of GBP significantly suppressed theta oscillation. Above all, chronic GBP altered these characteristics to reverse depression-like behaviors.ConclusionThe present study confirmed that the tonic firing activity of VTA DA neurons, but not the burst firing activity, was the key factor in peripheral neuropathy–induced depression. Chronic GBP regulated the firing pattern of DA neurons and decreased theta oscillation in VTA to treat pain-related depression. This variation tendency of electrophysiological characteristics of VTA DA neurons and theta oscillation in VTA might represent an attempt to cope with pain-related negative mood disorder.

Effective Dosage of Midazolam to Erase the Memory of Vascular Pain During Propofol Administration

Intravenous sedation with propofol is often administered to anxious patients in dental practice. Pain on injection of propofol is a common adverse effect. This study aimed to determine the age-adjusted doses of midazolam required to erase memory of vascular pain of propofol administration and assess whether the Ramsay Sedation Scale (RSS) after the pretreatment of midazolam was useful to predict amnesia of the vascular pain of propofol administration. A total of 246 patients with dental phobia requiring dental treatment under intravenous sedation were included. Patients were classified according to their age: 30s, 40s, 50s, and 60s. Three minutes after administration of a predetermined dose of midazolam, propofol was infused continuously. After completion of the dental procedure, patients were interviewed about the memory of any pain or discomfort in the injection site or forearm. The dosage of midazolam was determined using the Dixon up-down method. The first patient was administered 0.03 mg/kg, and if memory of vascular pain remained, the dosage was increased by 0.01 mg/kg for the next patient, and then if the memory was erased, the dosage was decreased by 0.01 mg/kg. The effective dosage of midazolam in 95% of each age group for erasing the memory of propofol vascular pain (ED95) was determined using logistic analysis. The accuracy of RSS to predict the amnesia of injection pain was assessed by receiver operating characteristic (ROC) analysis. The ED95 of midazolam to erase the memory of propofol vascular pain was 0.061 mg/kg in patients in their 30s, 0.049 mg/kg in patients in their 40s, 0.033 mg/kg in patients in their 50s, and 0.033 mg/kg in patients in their 60s. The area under the ROC curve was 0.31. The ED95 of midazolam required to erase the memory of propofol vascular pain demonstrated a downward trend with age. On the other hand, it was impossible to predict the amnesia of propofol vascular pain using the RSS.

ED50 of sevoflurane for I-Gel removal in anesthetized children in cataract surgeries using subtenon block.

Objective:The aim of this study was to determine the minimum concentration of sevoflurane required for I-Gel removal in 50% children undergoing elective cataract surgery.Design:A prospective observational study.Setting:A single tertiary care surgical center.Materials and Methods:Our study enrolled 20 American Society of Anesthesiologists I and II children aged 2-10 years, undergoing elective cataract surgery. Anesthesia was induced with sevoflurane and oxygen/nitrous oxide mixture and a size 2 I-Gel was inserted. A subtenon block was administered in all children before surgical incision. Sevoflurane was used for maintenance of anesthesia. Predetermined end-tidal concentration of sevoflurane was maintained for 10 min at the end of surgery before I-Gel removal was attempted. End-tidal concentrations were increased/decreased using the Dixon up-down method (with 0.2% as a step size) in the next patient depending on the previous patient's response. Patient responses to I-Gel removal were classified as “movement” or no “movement”.Results:Minimum concentration of sevoflurane required for successful removal of a I-Gel in 50% (ED50) and 95% (ED95) of children was 0.44% (95% confidence interval [CI], 0.34-0.52%) and 0.77% (95% CI, 0.63-1.2%), respectively.Conclusion:A very low end-tidal concentration of sevoflurane (ED50 of 0.44% ED95 of 0.77%) is required for I-Gel removal in children in cataract surgery with the supplementation of subtenon block.

Effective dose 50 of desflurane for laryngeal mask airway removal in anaesthetized children in cataract surgeries with subtenon block.

Background:Quantification of the depth of desflurane anesthesia required for laryngeal mask airway (LMA) removal in children has been done with the use of intravenous fentanyl or caudal anesthesia. This study aimed to determine the end-tidal concentration of desflurane required for LMA removal in children without the use of caudal or opioid analgesia in children undergoing elective cataract surgery.Materials and Methods:Our study enrolled 25 American Society of Anesthesiologists I and II children aged 2-10 years, undergoing elective cataract surgery. Anesthesia was induced with sevoflurane and oxygen/nitrous oxide using face mask and a size 2 LMA inserted. A subtenon block was administered in all children before surgical incision. Desflurane was used for maintenance of anesthesia. Predetermined end tidal concentration of desflurane was maintained for 10 min at the end of surgery before LMA removal was attempted. End tidal concentrations were increased/decreased using the Dixon up-down method (with 0.5% as a step size) in the next patient depending on the previous patient's response. Patient responses to LMA removal were classified as “movement” or “no movement.”Results:50% effective dose (ED50) for successful removal of the LMA with desflurane in the presence of subtenon block was 3.6% (3.20-3.97%) and that the 95% ED95 was 4.648% (4.15-6.47%).Conclusion:Laryngeal mask airway removal can be successfully accomplished in 50% and 95% anesthetized children at 3.6% and 4.65% end-tidal desflurane concentration.

The lowest effective intracuff pressure of the esophagus obstruction tube to prevent reflux of gastric contents: a study on rabbits

To determine the lowest effective cuff pressure of the esophageal obstruction tube to prevent reflux of gastric contents in rabbits. Twenty-two New Zealand white rabbits (2.0-2.5 kg) were anesthetized. An esophageal obstruction tube, an esophageal observation tube, and a gastric tube were inserted into the esophagus and stomach, respectively. Normal saline containing methylene blue was injected into the stomach for an animal model of gastric contents reflux. Possible saline reflux was observed through the esophageal observation tube. It was considered "regurgitation" when the saline flowed out, and "no regurgitation" when the saline did not. When a "regurgitation" result was obtained in a particular rabbit, the intracuff pressure was increased by 10 cm H(2)O in the following rabbit and vice versa. The trial was not terminated until six crossover points were observed from "no regurgitation" to "regurgitation." A probit regression model was used to analyze the effective intracuff pressure of the esophagus obstruction tube after 50 % and 95 % of the rabbits showed no reflux. The lowest effective intracuff pressure to prevent reflux of gastric contents in 50 % of rabbits from the Dixon up-down method was 61.67 ± 8.16 cm H(2)O. The intracuff pressures at which there was 50 % and 95 % probability of lack of gastric contents reflux from a probit regression model were 61.95 and 74.39 cm H(2)O, respectively. The insertion of an esophageal obstruction tube before endotracheal intubation can be an acceptable method for preventing the reflux of gastric contents in most rabbits under light anesthesia.

Minimum alveolar concentration of desflurane with caudal analgesia for laryngeal mask airway removal in anesthetized children

Regional blocks have been shown to decrease the requirement of anesthetic agents. This study was conducted to determine the optimal endtidal concentrations of desflurane for removal of Laryngeal mask airway in children in presence of caudal block. Twenty-two children of ASA status I between the age group of 2-10 year undergoing infraumbilical surgery were enrolled in the study. General anesthesia was induced with sevoflurane and oxygen given via mask and laryngeal mask airway inserted. Caudal injection of bupivacaine 0.25%, 1 ml·kg(-1) was administered according to Armitage regimen. Desflurane was used for maintenance of anesthesia. Predecided endtidal concentration of desflurane was maintained for 10 min at the end of surgery and laryngeal mask airway removed. Target concentration in the next patient was thereafter determined by the Dixon up-down method (with 0.5% as a step size). 5% endtidal concentration was kept as the starting concentration. If removal of laryngeal mask airway was not associated with any coughing, teeth clenching, gross purposeful movement, breath holding or laryngospasm, during or within 1 min after removal, it was considered as successful. In the presence of caudal analgesia, endtidal concentration of desflurane required for successful laryngeal mask airway removal in 50% (ED50) children was 3.39 ± 0.38% by Dixon's method. Laryngeal mask airway can be successfully removed in 50% of anesthetized children without coughing, moving, or any other airway complications at an endtidal desflurane concentration of 3.4% in the presence of caudal analgesia.

Estimating Efficacy and Drug ED50's Using von Frey Thresholds: Impact of Weber's Law and Log Transformation

The use of von Frey filaments, originally developed by Maximilian von Frey, has become the cornerstone for assaying mechanical sensitivity in animal models and is widely used for human assessment. While there are certain limitations associated with their use that make comparisons between studies not straightforward at times, such as stimulus duration and testing frequency, von Frey filaments provide a good measurement of mechanosensation. Here we describe the application of von Frey filaments to testing in animal models, specifically with respect to determining changes in sensory thresholds in a pain state using the Dixon up-down method. In a literature survey, we found that up to 75% of reports using this method analyze the data with parametric statistical analysis and of those that used nonparametric analysis, none took into account that mechanical sensation is perceived on a logarithmic scale (Weber's Law) when calculating efficacy. Here we outline a more rigorous analysis for calculating efficacy and ED50's from von Frey data that incorporates Weber's Law. We show that this analysis makes statistical and biological sense and provide a specific example of how this change affects data analysis that brings results from animal models more in line with clinical observations. PerspectiveThis focus article argues that analyzing von Frey paw withdrawal threshold data obtained by using the Dixon up-down method without considering Weber's Law is inappropriate. An analysis method that incorporates how mechanical sensation is perceived and how its application brings results from animal models more in line with clinical data is presented.

ED50 of desflurane for laryngeal mask airway removal in anaesthetised adults

Previous estimates for the end-tidal concentration of desflurane that allows removal of the laryngeal mask airway in 50% of anaesthetised adults (ED50) have ranged from 2.1% to 5.3%. To assess which value is correct, we studied 32 female patients (aged 30-50 years) undergoing intracavity caesium implants for cervical carcinoma under general anaesthesia. Anaesthesia was induced with propofol 2-3 mg.kg(-1) and maintained with desflurane in a 50% nitrous oxide-oxygen mixture. At the end of surgery, a predetermined target end-tidal desflurane concentration (starting at 4%) was maintained for 10 min using Dixon's up-down method and the laryngeal mask airway was removed. The target end-tidal concentration in the next patient was increased or decreased by 0.5% depending upon the response of the previous patient. Removal of the laryngeal mask airway without coughing, clenching, biting, movement or any adverse airway event during or within 1 min after removal was considered to be successful. We found that the laryngeal mask airway can be successfully removed in 50% (ED50) and 95% (ED95) of the anaesthetised adults at end-tidal desflurane concentrations of 2.4% (95% CI 1.3-2.9) and 3.8% (3.1-9.6), respectively.

Minimum alveolar concentrations of sevoflurane for maintaining bispectral index below 50 in children

To determine minimum alveolar concentration (MAC) of sevoflurane for maintaining bispectral index (BIS) below 50 (MAC(BIS50) ) in children. MAC(BIS50) of sevoflurane in adults was reported to be 0.97%, which has not been elucidated in children. 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. MAC(BIS50) of sevoflurane was 2.83% (95% confidence intervals: 2.70-3.14) in children. 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.

The end-tidal desflurane concentration for smooth removal of the laryngeal mask airway in anaesthetised adults

The end-tidal desflurane concentration required for smooth removal of the laryngeal mask airway (LMA) has not been established. Therefore, we aimed to find the end-tidal desflurane concentration for safe, smooth, and uncomplicated LMA removal. The study was approved by the Ethical Committee of the Ministry of Health, Diskapi Yildirim Beyazit Research and the Training Hospital, Ankara, Turkey. All patients provided written consent. A total of 23 adults, 18-60 years of age and American Society of Anesthesiologists physical status class I, who had been scheduled for urological surgery were included in the study. The intravenous induction of anaesthesia was performed with propofol 2.5 mg kg⁻¹ and remifentanil 10 μg within 30 s. The LMA was inserted. Maintenance of anaesthesia was provided by desflurane, with nitrous oxide and oxygen. The LMA was removed at predetermined end-tidal desflurane concentrations at the end of surgery. The concentration at which LMA removal was attempted was determined by Dixon's up-down method with 0.5% as the step size. When LMA removal was accomplished without coughing, teeth clenching, gross purposeful movements, breath holding, laryngospasm, and desaturation to SpO(2) less than 90%, it was considered a smooth (successful) removal. For smooth removal of the LMA, end-tidal desflurane EC50 was 2.1% [95% confidence interval (CI) 1.1-2.9%], and the EC95 value was 3.9% (95% CI 3.1-7.9%). The EC95 of end-tidal desflurane for the smooth removal of the LMA is 3.9%. LMA removal in adults receiving desflurane may be possible at approximately 0.7 minimum alveolar concentration.

Potency of Mephentermine for Prevention of Post-spinal Hypotension

This study was designed to determine the minimum effective dose (ED50) of mephentermine for prevention of post-spinal hypotension in women undergoing elective caesarean section. Dixon's up-down method of sequential allocation was used to determine the patient's dose of vasopressor drug. In our previous study, mephentermine appeared to be much more potent than ephedrine, so the present study was conducted using a lower initial dose and smaller dose interval for this vasopressor. Following administration of spinal anaesthesia, a prophylactic infusion of mephentermine was started with 5 mg infused over a period of 30 minutes as the initial dose and a dose interval of 1 mg. The ED50 of mephentermine of 3.7 mg (95% confidence interval 2.4 to 5.7 mg) was much less than that of ephedrine, as calculated in our previous study using the same methodology. Using these values gives a potency ratio of ephedrine to mephentermine of 1:6.8 (95% confidence interval 6.0 to 7.5).

MAC‐awake of sevoflurane in children

Age influences the potency of anesthetic agents, but there is little information on how age influences MAC-awake. MAC-awake may be an important aspect of anesthesia potency for the prevention of awareness during anesthesia. The aim of this study was to measure MAC-awake in a range of ages in children. After institutional ethics approval and informed parental consent 60 children were enrolled; 20 in each of three age groups (2 to <5, 5 to <8 and 8-12 years). Children were excluded if they had opioids, sedative premedication or a procedure likely to cause any residual discomfort. All children had sevoflurane anesthesia. At the end of the procedure the sevoflurane was decreased to the target concentration. Once the target endtidal concentration was achieved it was maintained for 10 min before a standard stimulus was applied and an observer determined if the child was awake. The Dixon up-down method was used to determine progression of subsequent concentrations and MAC-awake (ED50) for the three age groups were obtained using the probit model. This study found evidence for a difference in ED50 between age groups (P = 0.008). The MAC-awake was highest in the youngest group (0.66%) and similar in the older groups (0.45% and 0.43%). Although MAC-awake changes with age, in the ages where awareness has been reported, MAC-awake was found to be relatively low, and therefore it seems unlikely that age-specific changes to MAC-awake are a cause for awareness in children aged 5-12 years.

Comparison of Potency of Ephedrine and Mephentermine for Prevention of Post-Spinal Hypotension in Caesarean Section

The dosages and potency of intravenous mephentermine for prevention of post-spinal hypotension are not available in English literature. This study was designed to determine the minimum effective dose (ED50) of mephentermine and to compare its potency with that of ephedrine for prevention of post-spinal hypotension in parturients undergoing caesarean section. Dixon's up-down method of sequential allocation was used for vasopressor doses. Following administration of spinal anaesthesia, patients received a prophylactic infusion with 50 mg infused over a period of 30 minutes as the initial dose and dose intervals of 5 mg, of either ephedrine or mephentermine. The ED50 of ephedrine was 25.0 mg (95% CI 15.5 to 40.4 mg). For mephentermine, the up-down method was abandoned due to the success of the minimum dose possible but the ED50 appeared to be less than 5 mg. In conclusion, the minimum effective dose of mephentermine is much less than that of ephedrine for prevention of post-spinal hypotension. Another trial with a lower starting dose and smaller dose interval of mephentermine is required to determine the potency ratio of mephentermine and ephedrine.

A Comparison of the End-Tidal Sevoflurane Concentration for Removal of the Laryngeal Mask Airway and Laryngeal Tube in Anesthetized Children

In this study we quantified and compared the optimal sevoflurane concentration required to prevent coughing or moving during or after removal of the laryngeal mask airway (LMA) and the laryngeal tube (LT) in anesthetized children. Forty unpremedicated children, aged 8 mo to 12 yr, were randomly allocated to receive the LMA or LT. General anesthesia was induced via mask with sevoflurane and the LMA or LT was inserted. Anesthesia was maintained with sevoflurane and oxygen. At the end of surgery, a predetermined end-tidal sevoflurane concentration was maintained for at least 10 min and the LMA or LT was removed. Using Dixon's up-down method, the concentration for LMA and LT removal was determined by adjusting the dose by a 0.2% increment. Success was defined by the absence of coughing, teeth clenching, gross purposeful movement, breath holding, laryngospasm, and desaturation. The end-tidal concentration of sevoflurane to achieve successful LMA removal in 50% of children was 1.90%, in 95% of children was 2.15%. For the LT, the concentrations were 1.83% and 2.00%. The 50% effective dose values did not differ significantly between groups. LMA and LT removal in 95% of anesthetized children (aged 8 mo to 12 yr) can be safely accomplished without coughing, moving, or any other airway complications at 0.86 and 0.80 minimum alveolar anesthetic concentration, respectively, and a similar concentration should be used for removal of the LT or LMA in children.

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

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. 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. The observed propofol effect target with 50% response plus sevoflurane (0.46% end-tidal concentration) was 1.2 microg/ml (95% confidence interval, 1.1-1.3 microg/ml). It was not significantly different from that predicted (1.5 microg/ml; 95% confidence interval, 1.2-1.7 microg/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 microg/ml (95% confidence interval, 4.8-6.0 microg/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 microg/ml; 95% confidence interval, 4.8-5.9 microg/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. Propofol and sevoflurane interact in a simple additive manner to produce LOC and immobility to surgical incision, suggesting a common mechanism or a single site of action. These clinical observations are consistent with a single site of interaction at the gamma-aminobutyric acid type A receptor.

Optimal End-Tidal Sevoflurane Concentration for the Removal of the Laryngeal Mask Airway in Anesthetized Adults

Sevoflurane provides smooth and rapid emergence from anesthesia and can be used when the removal of a laryngeal mask airway (LMA) is required in anesthetized patients. We sought to determine the optimal end-tidal concentrations of sevoflurane required for the removal of LMA in anesthetized adults. We studied 35 adults, aged 22-64 years old with an ASA physical status I or II, who were undergoing perineal surgery. General anesthesia was induced with thiopental, and the LMA was then inserted. Anesthesia was maintained with sevoflurane, oxygen, and air. After the surgery, the target concentration was maintained for at least 10 min, and then the LMA was removed. Each target concentration at the time of removal was predetermined by the Dixon up-down method (with 0.1% as a step size) starting at 1.7% end-tidal concentration of sevoflurane. The LMA removal was considered successful when there was no coughing, clenching of teeth, or gross purposeful movements during or within 1 min after removal and also if there was no breath holding, laryngospasm, or desaturation after removal. The end-tidal concentration of sevoflurane to achieve successful LMA removal in 50% of adults was 0.99% +/- 0.09% (mean +/- SD) and in 95% of adults was 1.18% (95% confidence limits, 1.07%-1.79%). In conclusion, we have determined that LMA removal in 50% and 95% of anesthetized adults can be safely accomplished without coughing, moving, or any other airway complications at 0.99% and 1.18% end-tidal concentrations of sevoflurane. Because the removal of the laryngeal mask airway (LMA) in the anesthetized state is required in some clinical situations, we sought to determine the end-tidal concentration of sevoflurane to safely remove the LMA in anesthetized adults.

The minimum alveolar concentration (MAC) of sevoflurane with and without nitrous oxide in elderly versus young adults

Study Objective: To determine the minimum alveolar concentration (MAC) of sevoflurane with and without 65% nitrous oxide (N 2O) in non-Asian patients at least 70 years of age, and in patients aged 18 to 35 years. Design: Randomized open-study design. The Dixon up-down method determined the target sevoflurane concentration for each patient. Setting: Operating rooms of a large university hospital. Patients: 27 ASA status I and II patients aged 18 to 35 years and 26 patients at least 70 years of age, who were free of any conditions or diseases that would interfere with MAC determination. Interventions: Unpremedicated patients breathed sevoflurane until the predetermined target end-tidal sevoflurane concentration was reached for at least 15 minutes before skin incision. Up-down sevoflurane increments were 0.25% after an initial target concentration of 2%. This continued until there were at least three crossover pairs in each of the four groups. Measurements and Main Results: Patients were observed for purposeful movement in response to a skin incision. End-tidal sevoflurane, N 2O and oxygen (O 2) concentrations were measured by a calibrated infrared analyzer. MAC was determined by logistic regression analysis. The MAC of sevoflurane in O 2/air for the mean age in each group was 2.6% in the younger group (age = 25 yr) and 1.45% in the elderly group (age = 76 yr). Nitrous oxide 65% decreased MAC about 50% in each group at any age studied. Conclusions: The MAC of sevoflurane determined in this study is similar to that determined in previous studies, including the MAC determined in an elderly Asian population. Increasing age and N 2O decrease sevoflurane MAC similarly to that determined with other volatile anesthetics.