Enantioselective capillary electrophoresis for pharmacokinetic analysis of methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in equines anesthetized with ketamine and isoflurane.

An enantioselective assay for the determination of methadone and its main metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in equine plasma based on capillary electrophoresis with highly sulfated γ-cyclodextrin as chiral selector and electrokinetic analyte injection is described. The assay is based on liquid/liquid extraction of the analytes at alkaline pH from 0.1 mL plasma followed by electrokinetic sample injection of the analytes from the extract across a buffer plug without chiral selector. Separation occurs cationically at normal polarity in a pH 3 phosphate buffer containing 0.16% (w/v) of highly sulfated γ-cyclodextrin. The developed assay is precise (intra- and interday RSD < 4% and < 7%, respectively), is capable to determine enantiomer levels of methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in plasma down to 2.5 ng/mL, and was successfully applied to monitor enantiomer drug and metabolite levels in plasma of a pony that was anesthetized with racemic ketamine and isoflurane and received a bolus of racemic methadone and a bolus followed by constant rate infusion of racemic methadone. The data suggest that the assay is well suited for pharmacokinetic purposes.

Elimination of Intracardiac Shunting Provides Stable Gas Anesthesia in Tortoises.

Inhalant anesthesia is challenging in chelonians due to a great capacity for breath-holding and an incomplete separation of the cardiac ventricle. Deoxygenated blood can recirculate back into systemic circulation by bypassing the lung in a process referred to as intracardiac right to left (R-L) shunting. Via electrocardiogram gated magnetic resonance imaging, a novel modality to investigate arterial flows in reptiles, intracardiac shunting and its elimination via atropine during gas anesthesia in tortoises (Chelonoidis carbonaria) was demonstrated. The great vessels of the heart were visualized confirming that after shunt-elimination, the flow (mean ± sd) in the pulmonary arteries increased significantly (54.6 ± 9.5 mL min-1 kg-1 vs 10.8 ± 3.4 mL min-1 kg-1; P < 0.008). Consequently, animals required significantly lower concentrations of inhaled anesthetics to maintain a stable anesthesia. To that end, the minimum anesthetic concentration (MAC) of isoflurane needed to maintain surgical anesthesia was measured. A significantly lower MAC was found after administration of atropine (mean MAC ± sd 2.2 ± 0.3% vs 3.2 ± 0.4%; P < 0.002). Previously, MAC has been indeterminable in chelonians likely due to intracardiac shunting, so this report constitutes the first MAC study performed in a tortoise.

Effects of three fentanyl plasma concentrations on the minimum alveolar concentration of isoflurane in Hispaniolan Amazon parrots (Amazona ventralis).

OBJECTIVE To determine effects of 3 plasma concentrations of fentanyl on the minimum alveolar concentration of isoflurane (MACiso) and cardiovascular variables in Hispaniolan Amazon parrots (Amazona ventralis). ANIMALS 6 adult parrots. PROCEDURES In phase 1, anesthesia was induced and maintained with isoflurane; intermittent positive-pressure ventilation was provided. The MACiso was determined for each bird by use of a bracketing method and supramaximal electrical stimulus. Fentanyl (20 µg/kg) was administered IV, and blood samples were collected over time to measure plasma fentanyl concentrations for pharmacokinetic calculations. In phase 2, pharmacokinetic values for individual birds were used for administration of fentanyl to achieve target plasma concentrations of 8, 16, and 32 ng/mL. At each concentration, MACiso and cardiovascular variables were determined. Data were analyzed with mixed-effects multilevel linear regression analysis. RESULTS Mean ± SD fentanyl plasma concentrations were 0 ng/mL, 5.01 ± 1.53 ng/mL, 12.12 ± 3.58 ng/mL, and 24.93 ± 4.13 ng/mL, and MACiso values were 2.09 ± 0.17%, 1.45 ± 0.32%, 1.34 ± 0.31%, and 0.95 ± 0.14% for fentanyl target concentrations of 0, 8, 16, and 32 ng/mL, respectively. Fentanyl significantly decreased MACiso in a dose-dependent manner. Heart rate and blood pressure significantly decreased at all fentanyl doses, compared with values for MACiso at 0 ng of fentanyl/mL. CONCLUSIONS AND CLINICAL RELEVANCE Fentanyl significantly decreased the MACiso in healthy Hispaniolan Amazon parrots, but this was accompanied by a depressive effect on heart rate and blood pressure that would need to be considered for application of this technique in clinical settings.

Effect of Bronchoconstriction-induced Ventilation-Perfusion Mismatch on Uptake and Elimination of Isoflurane and Desflurane.

BACKGROUND: Increasing numbers of patients with obstructive lung diseases need anesthesia for surgery. These conditions are associated with pulmonary ventilation/perfusion (VA/Q) mismatch affecting kinetics of volatile anesthetics. Pure shunt might delay uptake of less soluble anesthetic agents but other forms of VA/Q scatter have not yet been examined. Volatile anesthetics with higher blood solubility would be less affected by VA/Q mismatch. We therefore compared uptake and elimination of higher soluble isoflurane and less soluble desflurane in a piglet model. METHODS: Juvenile piglets (26.7 ± 1.5 kg) received either isoflurane (n = 7) or desflurane (n = 7). Arterial and mixed venous blood samples were obtained during wash-in and wash-out of volatile anesthetics before and during bronchoconstriction by methacholine inhalation (100 µg/ml). Total uptake and elimination were calculated based on partial pressure measurements by micropore membrane inlet mass spectrometry and literature-derived partition coefficients and assumed end-expired to arterial gradients to be negligible. VA/Q distribution was assessed by the multiple inert gas elimination technique. RESULTS: Before methacholine inhalation, isoflurane arterial partial pressures reached 90% of final plateau within 16 min and decreased to 10% after 28 min. By methacholine nebulization, arterial uptake and elimination delayed to 35 and 44 min. Desflurane needed 4 min during wash-in and 6 min during wash-out, but with bronchoconstriction 90% of both uptake and elimination was reached within 15 min. CONCLUSIONS: Inhaled methacholine induced bronchoconstriction and inhomogeneous VA/Q distribution. Solubility of inhalational anesthetics significantly influenced pharmacokinetics: higher soluble isoflurane is less affected than fairly insoluble desflurane, indicating different uptake and elimination during bronchoconstriction.

Coronary Sinus Isoflurane Concentration in Cardiac Surgery.

OBJECTIVE: Volatile anesthetic agents such as isoflurane may be associated with fewer adverse myocardial events compared with total intravenous anesthesia in cardiac surgery. The authors aimed to determine whether reasonable isoflurane concentrations at tissue level were being achieved to protect the myocardium using this agent. The isoflurane concentration in myocardium has never been measured. The primary aim was to sample coronary sinus (CS) blood and measure its isoflurane concentration. Secondary aims were to determine whether the CS blood concentration would equilibrate with the arterial blood concentration and the relationship of CS blood concentration with oxygenator exhaust isoflurane concentrations during cardiopulmonary bypass (CPB). DESIGN: Prospective, observational study. SETTING: Single-center university hospital. PARTICIPANTS: The study comprised 23 patients undergoing cardiac surgery using CPB and isoflurane. MEASUREMENTS AND MAIN RESULTS: Shortly after initiation of CPB and insertion of a CS retrograde cardioplegia catheter but before aortic cross-clamping, CS blood was aspirated, followed by radial artery blood, which then were analyzed for isoflurane with gas chromatography and mass spectrometry. The oxygenator exhaust isoflurane level was measured with an anesthetic gas analyzer. The mean arterial and CS isoflurane concentrations were 87.7 ± 50.1 and 73.0 ± 42.9 µg/mL, respectively. There was a significant mean difference of 14.7 µg/mL (95% confidence interval 6.7-22.8) between CS and arterial isoflurane concentrations. Oxygenator exhaust isoflurane levels were correlated positively with those in the CS blood (r = 0.68, p < 0.001) and arterial blood (r = 0.72, p < 0.001). CONCLUSIONS: This was the first study in which CS blood was sampled and measured for isoflurane concentration. The CS isoflurane concentration could be estimated from the isoflurane concentration in the oxygenator exhaust gas. However, the value of this relationship is limited because the CS isoflurane concentration does not accurately represent its myocardial levels during CPB.

The decrease of NMDAR subunit expression and NMDAR EPSC in hippocampus by neonatal exposure to desflurane in mice.

Desflurane is one of the third generation inhaled anesthetics and can be used in obstetric and pediatric medicine. However, effects of exposure to desflurane on neonatal brain are largely unknown. In this work, 6-day-old C57BL/6J mice were exposed to 1MAC or 1.5MAC desflurane for 2h. When the mice were 28-day-old, the open-field, spontaneous alternation Y-maze and fear conditioning tests were performed to evaluate general activity, working memory and long term memory, respectively. Levels of NMDAR subunits NR1, NR2A, and NR2B expression in hippocampus were evaluated by western blot. NMDAR-mediated excitatory postsynaptic current (EPSC) in mouse hippocampal slice was recorded by whole-cell patch clamp record. Mice exposed to 1.5MAC desflurane had significantly impaired working memory and fear conditioning memory. The protein expression of NMDAR subunits (NR1, NR2B) and NMDAR-mediated EPSC in hippocampus were significantly decreased. However no significant difference was detected between mice exposed to 1.0MAC desflurane and control mice. In conclusion, in an animal model, 6-day-old mice exposed to 1.5MAC desflurane have significant impairments in working memory and contextual fear memory at postnatal day 28, and the decrease of NMDAR subunits expression and NMDAR EPSC in hippocampus may be involved in this process.

Sevoflurane and Isoflurane-Pharmacokinetics, Hemodynamic Stability, and Cardioprotective Effects During Cardiopulmonary Bypass.

OBJECTIVES: This study aimed to evaluate the pharmacokinetic profiles of sevoflurane and isoflurane during use of minimized extracorporeal circulation to perform coronary artery bypass graft surgery. Furthermore, cardiovascular stability during bypass and the postoperative release of troponins were evaluated. DESIGN: Prospective, randomized study. SETTING: University hospital. PARTICIPANTS: The study comprised 31 adult patients undergoing coronary artery bypass grafting. INTERVENTIONS: The pharmacokinetic measurements of the concentration of the volatile anesthetics in the arterial and venous blood, air inlet, air outlet, and gas exhaust of the extracorporeal circulation were recorded. Secondary end-points were cardiovascular stability during bypass, amount of postoperative release of troponin, time to extubation, time to discharge from the intensive care unit and the hospital, and 30-day mortality. MEASUREMENTS AND MAIN RESULTS: Thirty patients completed the protocol. The pharmacokinetics of isoflurane and sevoflurane were almost identical, with a rapid wash-in (time to reach 50% of arterial steady state) concentration of 0.87±0.97 minutes and 1.14±0.35 minutes for isoflurane and sevoflurane, respectively, and a biphasic venous elimination with a terminal half-life of approximately 10 minutes for both compounds. There was a correlation between the gas inlet and the gas exhaust of the extracorporeal circulation. No difference in cardiovascular stability was found. High-sensitivity troponin concentrations on the first postoperative morning were 0.355±0.312 µg/mL and 0.225±0.111 µg/mL in the isoflurane and sevoflurane groups, respectively (p = 0.147). CONCLUSIONS: The study found similar pharmacokinetics regarding wash-in and wash-out for sevoflurane and isoflurane. In addition, no difference in cardiovascular stability was found. The markers of cardiac damage were not different between the two anesthetics. Based on these data, sevoflurane and isoflurane might be used equivalently in patients undergoing coronary artery bypass graft surgery with extracorporeal circulation.

Comparison of the effects of inhalational anesthesia with desflurane and total intravenous anesthesia on cardiac biomarkers after aortic valve replacement.

OBJECTIVE (S): The aim of this study was to compare the effects of using inhalational anesthesia with desflurane with that of a total intravenous (iv) anesthetic technique using midazolam-fentanyl-propofol on the release of cardiac biomarkers after aortic valve replacement (AVR) for aortic stenosis (AS). The specific objectives included (a) determination of the levels of ischemia-modified albumin (IMA) and cardiac troponin I (cTnI) as markers of myocardial injury, (b) effect on mortality, morbidity, duration of mechanical ventilation, length of Intensive Care Unit (ICU) and hospital stay, incidence of arrhythmias, pacing, cardioversion, urine output, and serum creatinine. Methodology and Design: Prospective randomized clinical study. SETTING: Operation room of a cardiac surgery center of a tertiary teaching hospital. PARTICIPANTS: Seventy-six patients in New York Heart Association classification II to III presenting electively for AVR for severe symptomatic AS. INTERVENTIONS: Patients included in the study were randomized into two groups and subjected to either a desflurane-fentanyl based technique or total IV anesthesia (TIVA). Blood samples were drawn at preordained intervals to determine the levels of IMA, cTnI, and serum creatinine. MEASUREMENTS AND MAIN RESULTS: The IMA and cTnI levels were not found to be significantly different between both the study groups. Patients in the desflurane group were found to had significantly lower ICU and hospital stays and duration of postoperative mechanical ventilation as compared to those in the TIVA group. There was no difference found in mean heart rate, urine output, serum creatinine, incidence of arrhythmias, need for cardioversion, and 30-day mortality between both groups. The patients in the TIVA group had higher mean arterial pressures on weaning off cardiopulmonary bypass as well as postoperatively in the ICU and recorded lower inotrope usage. CONCLUSION: The result of our study remains ambiguous regarding the overall protective effect of desflurane in patients undergoing AVR although some benefit in terms of shorter duration of postoperative mechanical ventilation, ICU and hospital stays, as well as cTnI, were seen. However, no difference in overall outcome could be clearly established between patients who received desflurane and those that were managed solely with IV anesthetic technique using propofol.

Venous blood gas analytes during isoflurane anesthesia in black-tailed prairie dogs (Cynomys ludovicianus).

OBJECTIVE: To describe changes in venous blood gas analytes during isoflurane anesthesia in black-tailed prairie dogs (Cynomys ludovicianus). DESIGN: Prospective study. ANIMALS: 16 black-tailed prairie dogs. PROCEDURES: Black-tailed prairie dogs were placed in an anesthesia chamber for induction of general anesthesia, which was maintained with isoflurane in oxygen delivered via mask. Immediately following anesthetic induction, a venous blood sample was obtained from the medial saphenous vein; a second venous blood sample was obtained just prior to anesthetic gas shutoff. An evaluation of venous blood gas analytes was performed on each sample. General linear mixed models with repeated measures were used for data analyses. RESULTS: Median anesthetic time was 90 minutes (range, 60 to 111 minutes). A significant increase from immediately after induction to completion of anesthesia was observed in Pco2 and mean blood chloride ion, BUN, and creatinine concentrations. A decrease in Po2, mean blood pH, and anion gap was observed from induction of anesthesia to completion. No significant differences during anesthesia were observed in mean base excess or blood bicarbonate, sodium, potassium, calcium, magnesium, blood glucose, lactate, and total CO2 concentrations. No complications occurred during or after anesthesia for any animal. CONCLUSIONS AND CLINICAL RELEVANCE: Examination of prairie dogs often requires general anesthesia, with isoflurane currently the inhalation agent of choice. Results suggested respiratory acidosis and relative azotemia may occur during isoflurane anesthesia of prairie dogs. Given the increased risk associated with anesthesia in small mammals and the propensity for respiratory disease in prairie dogs, insight into physiologic changes associated with isoflurane anesthesia in healthy prairie dogs can aid in perioperative evaluation and anesthetic monitoring in this rodent species.

Blood/Gas partition coefficients for isoflurane, sevoflurane, and desflurane in a clinically relevant patient population.

BACKGROUND: The blood/gas partition coefficient of a certain volatile anesthetic is of clinical importance because it determines its velocity of uptake into and elimination from the body of a patient and thus its pharmacokinetic behavior. To date, the blood/gas partition coefficients of isoflurane, sevoflurane, and desflurane have been measured in small numbers of subjects or in particular study groups, for example, healthy volunteers, patients experiencing a common kind of disease, or mothers immediately after giving birth. The objective of this study was to determine the blood/gas partition coefficients of these volatile anesthetics at 37°C in a larger clinically relevant and adult patient population. Furthermore, we tested whether age, gender, body mass index, hemoglobin concentration, or hematocrit had an influence on the coefficients. METHODS: Blood samples were taken from 120 fasting operative patients with ASA physical status I to III and aged 19 to 86 years. All subjects were randomly enrolled in study groups for the separate determinations of the blood/gas partition coefficients of isoflurane (n = 41), sevoflurane (n = 41), and desflurane (n = 38) by headspace gas chromatography. To check the quality of the measurements, we determined the distilled water/gas partition coefficients of those anesthetics and compared them with previously published values. RESULTS: We found a blood/gas partition coefficient of 1.45 ± 0.12 (mean ± SD) for isoflurane, 0.74 ± 0.06 for sevoflurane, and 0.57 ± 0.04 for desflurane. Values of this study are 5.07%, 12.12%, and 7.55% higher for isoflurane, sevoflurane, and desflurane, respectively, than the previously published mean values (all P ≤ 0.001). There were only trends for small correlations between the blood/gas partition coefficient of isoflurane and hemoglobin concentration (Pearson r = 0.32; P = 0.041) and hematocrit (r = 0.37; P = 0.016). We found no other potentially significant correlations of the partition coefficients with patient age, body mass index, hemoglobin concentration, or hematocrit (all remaining P > 0.069). Furthermore, the coefficients did not differ significantly between female and male patients. The evaluation of the distilled water/gas partition coefficients of isoflurane (0.59 ± 0.04), sevoflurane (0.37 ± 0.04), and desflurane (0.27 ± 0.03) proved the validity of the gas chromatography method used in this study. CONCLUSIONS: The blood/gas partition coefficients of the modern volatile anesthetics, in particular, those of sevoflurane and desflurane, may be higher than that has been hitherto reported. Therefore, their uptake and elimination may occur more slowly in some patients than has been supposed. The blood/gas partition coefficients of isoflurane, sevoflurane, and desflurane measured in this study appear to be representative because they were determined in a clinically and numerically relevant patient cohort.

Volatile anaesthetics reduce neutrophil inflammatory response by interfering with CXC receptor-2 signalling.

BACKGROUND: Growing evidence suggests a protective effect of volatile anaesthetics in ischaemia-reperfusion (I/R)-injury, and the accumulation of neutrophils is a crucial event. Pro-inflammatory cytokines carrying the C-X-C-motif including interleukin-8 (IL-8) and CXC-ligand 1 (CXCL1) activate CXC receptor-1 (CXCR1; stimulated by IL-8), CXC receptor-2 (CXCR2; stimulated by IL-8 and CXCL1), or both to induce CD11b-dependent neutrophil transmigration. Inhibition of CXCR1, CXCR2, or both reduces I/R-injury by preventing neutrophil accumulation. We hypothesized that interference with CXCR1/CXCR2 signalling contributes to the well-established beneficial effect of volatile anaesthetics in I/R-injury. METHODS: Isolated human neutrophils were stimulated with IL-8 or CXCL1 and exposed to volatile anaesthetics (sevoflurane/desflurane). Neutrophil migration was assessed using an adapted Boyden chamber. Expression of CD11b, CXCR1, and CXCR2 was measured by flow cytometry. Blocking antibodies against CXCR1/CXCR2/CD11b and phorbol myristate acetate were used to investigate specific pathways. RESULTS: Volatile anaesthetics reduced CD11b-dependent neutrophil transmigration induced by IL-8 by >30% and CD11b expression by 18 and 27% with sevoflurane/desflurane, respectively. This effect was independent of CXCR1/CXCR2 expression and CXCR1/CXCR2 endocytosis. Inhibition of CXCR1 signalling did not affect downregulation of CD11b with volatile anaesthetics. Blocking of CXCR2-signalling neutralized effects by volatile anaesthetics on CD11b expression. Specific stimulation of CXCR2 with CXCL1 was sufficient to induce upregulation of CD11b, which was impaired with volatile anaesthetics. No effect of volatile anaesthetics was observed with direct stimulation of protein kinase C located downstream of CXCR1/CXCR2. CONCLUSION: Volatile anaesthetics attenuate neutrophil inflammatory responses elicited by CXC cytokines through interference with CXCR2 signalling. This might contribute to the beneficial effect of volatile anaesthetics in I/R-injury.

Determinação da concentração alveolar mínima do isofluorano em catetos (Tayassu tajacu) / Isoflurane minimum alveolar concentration in collared peccary (Tayassu tajacu)

A anestesia inalatória vem sendo amplamente difundida na medicina veterinária, no entanto seu uso em animais selvagens ainda é restrito, não sendo observado nenhum estudo referente à sua utilização na espécie Tayassu tajacu. O objetivo da pesquisa foi determinar a concentração alveolar mínima (CAM) do isofluorano em catetos e apresentar os efeitos desta administração sobre as variáveis hemodinâmicas e respiratórias, como também a qualidade da recuperação anestésica. Utilizou-se 10 animais, machos, com idade variando de 1 a 3 anos oriundos do Centro de Multiplicação de Animais Silvestres da Universidade Federal Rural do Semi-Árido, Brasil. Todos os animais tiveram anestesia induzida com 7mg.kg-1 de propofol e posteriormente foram conectados a circuito anestésico com isofluorano e oxigênio 100 por cento. O estímulo noceptivo supramáximo adotado foi pinçamento interdigital, o qual era realizado após 15 minutos de espera para cada concentração de isofluorano fornecida. Ao ser observada resposta negativa frente ao estímulo a concentração era reduzida em 20 por cento, quando verificada resposta positiva o estímulo era cessado, calculando-se a partir daí o valor da CAM. [...] A recuperação anestésica foi tranquila e rápida. Concluiu-se que a CAM do isofluorano para catetos foi maior que a observada em espécies afins. O isofluorano pode ser utilizado nesta espécie, sendo considerado seguro e eficaz. A recuperação dos animais após anestesia com isofluorano foi livre de excitação.

Inhalation anesthesia has been widespread in veterinary medicine. Nevertheless, its use in wild animals is still limited, having no studies on its use been observed in the species. The objective of the research was to determine the isoflurane minimum alveolar concentration (MAC) in peccaries and present the effects of its administration on the hemodynamic and respiratory variables, as well as data concerning the anesthesia recovery. The study used 10 male animals with age ranging from one to three years, from the Centro de Multiplicação de Animais Silvestres of Universidade Federal Rural do Semi-Árido, Brazil. All the animals had anesthesia induced with propofol 7mg.kg-¹, were intubated and connected to the anesthetic circuit with isoflurane and 100 percent oxygen. The supramaximal noxious stimulation used was the interdigital pinch, which was performed after 15 minutes of waiting for each provided isoflurane concentration. When negative response to the stimulus was observed, the concentration was reduced by 20 percent; when positive response was verified, the stimulus was stopped, being the CAM value calculated from that point. [...] Recovery was quiet and smooth. It was concluded that the isoflurane MAC for peccaries was greater than that observed in related species. Isoflurane can be used in this species, being considered safe and effective. The animals' recovery after anesthesia with isoflurane was free from excitement.

Duration effect of desflurane anesthesia and its awakening time and arterial concentration in gynecologic patients.

OBJECTIVES: To determine the awakening arterial blood concentration of desflurane and its relationship with the end-tidal concentration during emergence from various durations of general anesthesia. METHOD: In total, 42 American Society of Anesthesiologists physical status class I-II female patients undergoing elective gynecologic surgery were enrolled. General anesthesia was maintained with fixed 6% inspiratory desflurane in 6 l min-1 oxygen until shutoff of the vaporizer at the end of surgery. One milliliter of arterial blood was obtained for desflurane concentration determination by gas chromatography at 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after the discontinuation of desflurane and at the time of eye opening upon verbal command, defined as awakening. Concentrations of inspiratory and end-tidal desflurane were simultaneously detected by an infrared analyzer. RESULTS: The mean arterial blood concentration of desflurane was 1.20% at awakening, which correlated with the awakening end-tidal concentration of 0.96%. The mean time from the discontinuation of desflurane to eye opening was 5.2 minutes (SD = 1.6, range 3-10), which was not associated with the duration of anesthesia (60-256 minutes), total fentanyl dose, or body mass index (BMI). CONCLUSIONS: The mean awakening arterial blood concentration of desflurane was 1.20%. The time to awakening was independent of anesthetic duration within four hours. Using well-assisted ventilation, the end-tidal concentration of desflurane was proven to represent the arterial blood concentration during elimination and could be a clinically feasible predictor of emergence from general anesthesia.

Duration effect of desflurane anesthesia and its awakening time and arterial concentration in gynecologic patients

OBJECTIVES: To determine the awakening arterial blood concentration of desflurane and its relationship with the end-tidal concentration during emergence from various durations of general anesthesia. METHOD: In total, 42 American Society of Anesthesiologists physical status class I-II female patients undergoing elective gynecologic surgery were enrolled. General anesthesia was maintained with fixed 6% inspiratory desflurane in 6 l min-1 oxygen until shutoff of the vaporizer at the end of surgery. One milliliter of arterial blood was obtained for desflurane concentration determination by gas chromatography at 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after the discontinuation of desflurane and at the time of eye opening upon verbal command, defined as awakening. Concentrations of inspiratory and end-tidal desflurane were simultaneously detected by an infrared analyzer. RESULTS: The mean arterial blood concentration of desflurane was 1.20% at awakening, which correlated with the awakening end-tidal concentration of 0.96%. The mean time from the discontinuation of desflurane to eye opening was 5.2 minutes (SD = 1.6, range 3-10), which was not associated with the duration of anesthesia (60-256 minutes), total fentanyl dose, or body mass index (BMI). CONCLUSIONS: The mean awakening arterial blood concentration of desflurane was 1.20%. The time to awakening was independent of anesthetic duration within four hours. Using well-assisted ventilation, the end-tidal concentration of desflurane was proven to represent the arterial blood concentration during elimination and could be a clinically feasible predictor of emergence from general anesthesia. .

Combination of remifentanil with isoflurane or propofol: effect on the surgical stress response.

BACKGROUND: Hormonal and metabolic changes following surgery are markers of the stress response to surgery. We compared hemodynamic parameters and stress response markers (glucose, cortisol, and C-reactive protein) in two groups of patients receiving either propofol or isoflurane combined with remifentanil for maintenance of anesthesia. METHODS: We randomly assigned 100 women (ASA I-II) scheduled for diagnostic gynecologic laparoscopy to receive either isoflurane (0.8% end-tidal) or propofol (100 mg/kg/min) in addition to remifentanil (0.25 mg/ kg/min). Heart rate and mean arterial pressure were recorded after induction, 30 seconds after intubation, at four time points after incision, and 60 min after surgery. Serum C-reactive protein, cortisol and glucose concentrations were measured before induction, one hour after incision, and one hour after surgery. RESULTS: After induction, heart rate decreased significantly from baseline in both groups, and remained below baseline until the end of surgery. Mean arterial pressure also decreased significantly in both groups. C-reactive protein levels were not significantly different between groups. In the propofol group, cortisol decreased significantly one hour after incision, but increased in the isoflurane group. Glucose increased significantly in both groups, but was significantly lower in the propofol group one hour after the incision and one hour after surgery. CONCLUSION: An anesthetic regimen combining propofol and remifentanil attenuates two indicators of the stress response more efficiently than a isoflurane - remifentanil combination.

Strain differences in cortical electroencephalogram associated with isoflurane-induced loss of consciousness.

INTRODUCTION: Previously observed increased sensitivity to noxious stimulation in the Dahl salt-sensitive rat strain (SS/JrHsdMcwi, abbreviated as SS) compared to Brown Norway rats (BN/NhsdMcwi abbreviated as BN) is mediated by genes on a single chromosome. The current study used behavioral and electrocortical data to determine if differences also exist between SS and BN rats in loss of consciousness. METHODS: Behavioral responses, including loss of righting, (a putative index of consciousness) and concurrent electroencephalogram recordings, in 12 SS and BN rats were measured during isoflurane at inhaled concentrations of 0, 0.3, 0.6, 0.8, 1.0 and 1.2%. RESULTS: In SS compared to BN rats, the mean ± SEM EC50 for righting was significantly less (0.65 ± 0.01% vs. 0.74 ± 0.02% inhaled isoflurane) and delta fraction in parietal electroencephalogram was enhanced 50-100% at all isoflurane levels during emergence. The frequency decay constant of an exponential fit of the parietal electroencephalogram spectrum graphed as a function of isoflurane level was three times less steep (mean ± SEM slope -57 ± 13 vs. -191 ± 38) and lower at each level of isoflurane in SS versus BN rats (i.e., shifted toward low frequency activity). Electroencephalogram differences between strains were larger during emergence than induction. CONCLUSIONS: Sensitivity is higher in SS compared to BN rats leading to unconsciousness at lower levels of isoflurane. This supports using additional strains in this animal model to study the genetic basis for differences in anesthetic action on mechanisms of consciousness. Moreover, induction and emergence appear to involve distinct pathways.

Pharmacokinetics of intravenous emulsified isoflurane in beagle dogs.

BACKGROUND: We previously demonstrated that i.v. emulsified isoflurane induces general anaesthesia in animals. In this study, we compared the pharmacokinetics of emulsified isoflurane given as i.v. bolus and as infusion in beagle dogs. METHODS: Sixteen beagle dogs were assigned randomly to a bolus group comprising three subgroups and an infusion group. The three bolus subgroups received 120, 150, or 180 mg kg(-1) of isoflurane and the infusion group received isoflurane at 12 mg kg(-1) min(-1) for 150 min. Isoflurane concentrations were determined by gas chromatography. The parameters involved in the pharmacokinetic model were calculated using the DAS ver1.0 software. RESULTS: A two-compartment model best described the data in both bolus and infusion groups. The half-lives of distribution [t(1/2α): 1.77 (0.57) min] and elimination [t(1/2ß): 17.66 (5.56) min] in the bolus group were shorter than those in the infusion group [14.12 (4.04) min, 58.21 (11.39) min, P<0.01]. The apparent volume of the central compartment [V(1), 0.377 (0.138) litre kg(-1)] in the bolus group was less than that in the infusion group [0.809 (0.077) litre kg(-1), P<0.01]. The total body clearance [Cl, 0.043 (0.032) litre kg(-1) min(-1)] in the bolus group was greater than that in the infusion group [0.028 (0.008) litre kg(-1) min(-1)]. CONCLUSIONS: A two-compartment model adequately describes the pharmacokinetics of emulsified isoflurane for both bolus and infusion. The resulting kinetic parameters differ mainly because of the increasing blood/gas partition coefficient and the sustained nature of the isoflurane partial pressure during infusion.

Hyperventilation accelerates the rise of arterial blood concentrations of desflurane in gynecologic patients.

OBJECTIVES: Under a constant inspired concentration, the uptake of a volatile anesthetic into the arterial blood should mainly be governed by alveolar ventilation, according to the assumption that the patient's cardiac output remains stable during anesthesia. We investigated whether ventilation volume affects the rate of desflurane uptake by examining arterial blood concentrations. METHOD: Thirty female patients were randomly allocated into the following three groups: hyperventilation, normal ventilation and hypoventilation. Hemodynamic variables were measured using a Finometer, inspiratory and end-tidal concentrations of desflurane were measured by infrared analysis, and the desflurane concentration in the arterial blood (Ades) was analyzed by gas chromatography. RESULTS: During the first 10 minutes after the administration of desflurane, the Ades was highest in the hyperventilation group, and this value was significantly different from those obtained for the normal and hypoventilation groups. In addition, hyperventilation significantly increased the slope of Ades-over-time during the first 5 minutes compared with patients experiencing normal ventilation and hypoventilation, but there were no differences in these slopes during the periods from 5-10, 10-20 and 20-40 minutes after the administration of desflurane. This finding indicates that there were no differences in desflurane uptake between the three groups after the first 5 minutes within desflurane administration. CONCLUSIONS: Hyperventilation accelerated the rate of the rise in Ades following desflurane administration, which was time-dependent with respect to different alveolar ventilations levels.

Hyperventilation accelerates the rise of arterial blood concentrations of desflurane in gynecologic patients

OBJECTIVES: Under a constant inspired concentration, the uptake of a volatile anesthetic into the arterial blood should mainly be governed by alveolar ventilation, according to the assumption that the patient's cardiac output remains stable during anesthesia. We investigated whether ventilation volume affects the rate of desflurane uptake by examining arterial blood concentrations. METHOD: Thirty female patients were randomly allocated into the following three groups: hyperventilation, normal ventilation and hypoventilation. Hemodynamic variables were measured using a Finometer, inspiratory and end-tidal concentrations of desflurane were measured by infrared analysis, and the desflurane concentration in the arterial blood (Ades) was analyzed by gas chromatography. RESULTS: During the first 10 minutes after the administration of desflurane, the Ades was highest in the hyperventilation group, and this value was significantly different from those obtained for the normal and hypoventilation groups. In addition, hyperventilation significantly increased the slope of Ades-over-time during the first 5 minutes compared with patients experiencing normal ventilation and hypoventilation, but there were no differences in these slopes during the periods from 5-10, 10-20 and 20-40 minutes after the administration of desflurane. This finding indicates that there were no differences in desflurane uptake between the three groups after the first 5 minutes within desflurane administration. CONCLUSIONS: Hyperventilation accelerated the rate of the rise in Ades following desflurane administration, which was time-dependent with respect to different alveolar ventilations levels.

Effect of dexmedetomidine on the minimum alveolar concentration of isoflurane in cats.

This study reports the effects of dexmedetomidine on the minimum alveolar concentration of isoflurane (MAC(iso) ) in cats. Six healthy adult female cats were used. MAC(iso) and dexmedetomidine pharmacokinetics had previously been determined in each individual. Cats were anesthetized with isoflurane in oxygen. Dexmedetomidine was administered intravenously using target-controlled infusions to maintain plasma concentrations of 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, and 20 ng/mL. MAC(iso) was determined in triplicate at each target plasma dexmedetomidine concentration. Blood samples were collected and analyzed for dexmedetomidine concentration. The following model was fitted to the concentration-effect data: [Formula in text] where MAC(iso.c) is MAC(iso) at plasma dexmedetomidine concentration C, MAC(iso.0) is MAC(iso) in the absence of dexmedetomidine, I(max) is the maximum possible reduction in MAC(iso), and IC(50) is the plasma dexmedetomidine concentration producing 50% of I(max). Mean ± SE MAC(iso.0), determined in a previous study conducted under conditions identical to those in this study, was 2.07 ± 0.04. Weighted mean ± SE I(max), and IC(50) estimated by the model were 1.76 ± 0.07%, and 1.05 ± 0.08 ng/mL, respectively. Dexmedetomidine decreased MAC(iso) in a concentration-dependent manner. The lowest MAC(iso) predicted by the model was 0.38 ± 0.08%, illustrating that dexmedetomidine alone is not expected to result in immobility in response to noxious stimulation in cats at any plasma concentration.