Ventilation/perfusion ratios measured by multiple inert gas elimination during experimental cardiopulmonary resuscitation.

BACKGROUND: During cardiopulmonary resuscitation (CPR) the ventilation/perfusion distribution (VA /Q) within the lung is difficult to assess. This experimental study examines the capability of multiple inert gas elimination (MIGET) to determine VA /Q under CPR conditions in a pig model. METHODS: Twenty-one anaesthetised pigs were randomised to three fractions of inspired oxygen (1.0, 0.7 or 0.21). VA/ Q by micropore membrane inlet mass spectrometry-derived MIGET was determined at baseline and during CPR following induction of ventricular fibrillation. Haemodynamics, blood gases, ventilation distribution by electrical impedance tomography and return of spontaneous circulation were assessed. Intergroup differences were analysed by non-parametric testing. RESULTS: MIGET measurements were feasible in all animals with an excellent correlation of measured and predicted arterial oxygen partial pressure (R(2) = 0.96, n = 21 for baseline; R(2) = 0.82, n = 21 for CPR). CPR induces a significant shift from normal VA /Q ratios to the high VA /Q range. Electrical impedance tomography indicates a dorsal to ventral shift of the ventilation distribution. Diverging pulmonary shunt fractions induced by the three inspired oxygen levels considerably increased during CPR and were traceable by MIGET, while 100% oxygen most negatively influenced the VA /Q. Return of spontaneous circulation were achieved in 52% of the animals. CONCLUSIONS: VA /Q assessment by MIGET is feasible during CPR and provides a novel tool for experimental purposes. Changes in VA /Q caused by different oxygen fractions are traceable during CPR. Beyond pulmonary perfusion deficits, these data imply an influence of the inspired oxygen level on VA /Q. Higher oxygen levels significantly increase shunt fractions and impair the normal VA /Q ratio.

Blood concentrations of enflurane before, during, and after hypothermic cardiopulmonary bypass.

OBJECTIVE: The purpose of this study was to determine blood concentrations of enflurane delivered via a membrane oxygenator during hypothermic cardiopulmonary bypass (CPB) with changes in the input enflurane concentration and temperature and to characterize the pharmacokinetics of enflurane washout during and after CPB. DESIGN: Blood enflurane concentrations were measured by gas chromatography before, during, and after CPB by using mean delivered enflurane concentrations of 0.5% v/v (group 1, n = 5), 0.8% (group 2, n = 7), and 1% (group 3, n = 14). SETTING: The investigation was performed in a teaching hospital setting. PARTICIPANTS: Twenty-six patients undergoing cardiac surgery requiring hypothermic CPB. INTERVENTIONS: Variations in input enflurane concentration in different patients plus blood sampling from the arterial side of the circuit for enflurane assay. MEASUREMENTS AND MAIN RESULTS: Median (25th and 75th percentiles) pre-CPB blood enflurane concentrations were 48 (25-50) mg/L, 52 (47-56) mg/L, and 115 (90-143) mg/L in groups 1 (0.5% v/v), 2 (0.8% v/v), and 3 (1% v/v), respectively. During hypothermia (28 degrees C) corresponding enflurane concentrations were 44 (31-53) mg/L, 56 (45-62) mg/L, and 145 (109-203) mg/L, respectively. For groups 1 and 2, there were no significant changes in blood enflurane compared with the corresponding pre-CPB value. However, for group 3, cooling resulted in a significant increase (p = 0.006) in blood enflurane. In all groups, enflurane concentrations after rewarming were similar to those in the pre-CPB period. CONCLUSIONS: It is concluded that exposure to enflurane concentrations greater than 0.8% during CPB can result in high blood concentrations.

Existence of reverse second gas effect with enflurane.

OBJECTIVE: To investigate the existence of 'reverse second gas effect' with enflurane and to find out any influence of the variables; age, gender, body weight and American society of anaesthesiologist (ASA) status of the patient over the existence of reverse second gas effect. METHODS: This double blinded randomized control trial included forty eight adult ASA I and II patients divided in two groups 'A' and 'B'. The existence of reverse second gas effect was investigated in terms of rate of decline of exhaled concentration of enflurane with and without nitrous oxide. Collected data included age, weight, gender, ASA status, rate of decline of exhaled enflurane, heart rate & blood pressure of patients during the research protocol. RESULTS: Independent 't' test was used to compare the rate of decline and exhaled concentration of enflurane with and without nitrous oxide (p = 0.22). 'T' test was also used (p = 0.45 & 0.97 respectively) to observe the influence of age and weight. For the influence of ASA status and gender, chi square test was applied (p = 0.99 and 0.77 respectively). CONCLUSION: From the results of our study, we concluded that reverse second gas effect does not exist with enflurane. Furthermore, no influence of the variables age, gender, ASA status and body weight could be found on the existence of reverse second gas effect.

Determination of volatile anesthetics isoflurane and enflurane in mouse brain tissues using gas chromatography-mass spectrometry.

INTRODUCTION: A method for determination of the volatile anesthetics, isoflurane, and enflurane in mouse brain tissues using headspace gas chromatography-mass spectrometry (GC-MS) is described. METHODS: Halothane was used as internal standard (I.S.). Brain samples were completely homogenized in ice-cold water and isoflurane, enflurane, and I.S. were extracted with headspace. One milliliter of headspace gas was injected onto the GC-MS and separation was achieved by using porous layer open tubular (PLOT) capillary column with a solid stationary phase (GSC). As a result, isoflurane, enflurane, and halothane were cleanly separated. RESULTS: The method demonstrated satisfactory recovery (72% and 76% for isoflurane and enflurane, respectively) and linear calibration ranges of 0.015-2.20 and 0.0152-3.94 microg/sample for isoflurane and enflurane, respectively. Reproducibility calculated as CV% was 3.3-3.9% for all intraday and interday determinations. The procedure was applied for quantitation of isoflurane and enflurane in about 300 mouse brain samples for genetic behavioral study. DISCUSSION: The method was achieved and shown to be effective.

Predictive performance of a physiological model for enflurane closed-circuit anaesthesia: effects of continuous cardiac output measurements and age-related solubility data.

BACKGROUND: The disposition of inhalation anaesthetics is governed by the factors described in the Fick principle. METHODS: We have recalibrated a previously validated physiological model for enflurane closed-circuit inhalation anaesthesia, using individual continuous cardiac output measurements as well as age-related enflurane solubility coefficients as inputs to the model. Two model versions using 'calculated' (Brody's formula) or 'measured' (thoracic electrical bioimpedance) cardiac output values, and two versions with 'standard' (fixed) or 'age-related' solubility coefficients were formulated. RESULTS: Data from 62 ophthalmic surgical patients were used to validate the predictive performance of the four model versions. The root mean squared errors (total error) and scatters (error variation) were similar with the extended model versions, but the group biases (systematic error component) were significantly less with the model versions that included age-related solubility compared with the versions using standard solubility coefficients (bias -0.76/-0.78% vs -3.44/-3.60%). CONCLUSION: The inclusion of age-related solubility coefficients but not of continuous cardiac output measurements improves the predictive performance of the physiological model for closed-circuit inhalation anaesthetic conditions in routine clinical practice.

Fresh gas flow is not the only determinant of volatile agent consumption: a multi-centre study of low-flow anaesthesia.

METHODS: Seven academic centres studied 302 patients, using desflurane, enflurane, halothane, or isoflurane using circle-systems and Dräger Julian anaesthetic machines, with fresh gas flows (V(F)) of 3, 1, and 0.5 litre min(-1). Volatile agent partial pressures in the breathing system were recorded and agent consumptions measured by weighing. RESULTS: At these flows, desflurane consumption depended on V(F). In contrast, halothane consumption was not influenced by V(F). Isoflurane and enflurane showed differences in consumption between flows of 0.5 and 3 litre min(-1). Stepwise linear regression suggested that besides V(F), other factors influenced consumption of the more soluble agents (sex, age, weight, height, altitude, and temperature). The partial pressure ratios were independent of V(F) for desflurane (end-tidal to fresh gas=0.8), but the ratios of the more soluble agents varied with V(F) (end-tidal to fresh gas=0.3-0.7). CONCLUSIONS: At V(F) that involves significant re-breathing, consumption of soluble agents depends only partially on V(F). These results can be explained using Mapleson's hydraulic analogue model.

Caudal anesthesia reduces the minimum alveolar concentration of enflurane for laryngeal mask airway removal in boys.

PURPOSE: To investigate the effects of caudal analgesia on the minimal alveolar concentration of enflurane for laryngeal mask airway (LMA) smooth extubation (MACex). METHODS: We studied 50 nonpremedicated children, aged three to ten years, ASA physical status I, undergoing surgery for hypospadias repair. After a sevoflurane inhalation induction, children were randomized to receive LMA insertion with or without ropivacaine caudal analgesia. At the end of surgery, a predetermined end-tidal enflurane concentration was achieved, and the LMA was removed by an anesthesiologist blinded to group allocation. Each concentration at which LMA extubation was attempted was predetermined by the up-and-down method (with 0.1% as the step size). When LMA removal was accomplished without coughing, clenching teeth or gross purposeful muscular movements during or within one minute after removal, it was considered successful. RESULTS: MACex of enflurane for LMA removal in the group without caudal anesthesia was 1.04% (95% confidence interval, 1.00-1.10) and the LMA MACex of enflurane in the group with caudal anesthesia was 0.74% (95% confidence interval, 0.63-0.81). Caudal analgesia significantly reduced enflurane requirements by 29% (95% confidence interval, 22-36%). CONCLUSION: In conclusion, caudal analgesia significantly reduced the LMA MACex of enflurane by approximately 29%. Possible mechanisms may be related to the analgesic effect of caudal blockade or to the sedative properties of neuraxial anesthesia.

Tissue solubility of four volatile anesthetics in fresh and frozen tissue specimens from swine.

OBJECTIVE: To determine tissue solubilities of desflurane, sevoflurane, enflurane, and halothane in swine and to evaluate the effects of freezing specimens on tissue solubility, SAMPLE POPULATION: Arterial blood samples and specimens of brain, heart, liver, kidney, muscle, and subcutaneous fat from 5 healthy female adult Chinese Meishan pigs. PROCEDURE: Each tissue specimen was divided into 2 parts. One part was used to measure tissue-gas partition coefficients immediately after collection. The other part was frozen at -20 C for 6 days prior to determination of tissue-gas partition coefficients. Tissue-gas and blood-gas partition coefficients were measured by use of gas chromatography, and tissue-blood partition coefficients were calculated. Regression analysis was performed to determine whether fat-gas partition coefficients were correlated with lean tissue-gas partition coefficients. RESULTS: Tissue-gas and blood-gas partition coefficients of halothane were greater than those of enflurane followed by coefficients of sevoflurane and desflurane. However, the order of anesthetic agents with the greatest to smallest tissue-blood partition coefficients was sevoflurane, halothane, enflurane, and desflurane. Muscle-gas partition coefficients of sevoflurane and enflurane, liver-gas partition coefficients of desflurane and halothane, and the kidney-gas partition coefficient of enflurane were significantly greater in frozen specimens, compared with fresh specimens. Lean tissue-gas partition coefficients of all 4 volatile anesthetics correlated directly with fat-gas partition coefficients. CONCLUSIONS AND CLINICAL RELEVANCE: The fat content of lean tissue is an important factor in determining the tissue solubility of volatile anesthetics. Freezing specimens before determination of tissue-gas partition coefficients may result in a false increase in tissue solubility.

Pharmacodynamic interaction of nitrous oxide with sevoflurane, desflurane, isoflurane and enflurane in surgical patients: measurements by effects on EEG median power frequency.

BACKGROUND AND OBJECTIVE: This study investigates the interaction of sevoflurane and nitrous oxide on EEG median power frequency of 2.5 Hz during surgery. METHODS: Sevoflurane concentrations required for electroencephalographic median power frequency between 2 and 3 Hz were measured in 25 patients during gynaecological laparotomies. Nitrous oxide was randomly administered at 0, 20, 40, 60 and 75 vol%, subsequently two different concentrations in each patient. The data were analysed using isobolographic analysis together with previously published data on nitrous oxide-isoflurane, -enflurane, or -desflurane interaction. RESULTS: The interaction is described by the equation: C volatile anaesthetic/C0 volatile anaesthetic + C N2O/C0 N2O=1 (C is the concentrations for a drug combination to achieve the desired effect; C0 is the concentration for single drug use). The parameters are C0 isoflurane=1.11 vol% (95% CI 1.03-1.19), C0 enflurane=1.64 (1.52-1.77), C0 desflurane=5.31 (4.92-5.73), C0 sevoflurane=2.12 (1.96-2.29), C0 N2O=174 (153-202). These parameters decrease by 6% (2.5-10) for every 10 years of patients' age > 40 years. CONCLUSIONS: The interaction is compatible with additivity. The potency of nitrous oxide to substitute the volatile anaesthetics is less than anticipated from previously reported MAC values.

The minimum alveolar concentration of enflurane for laryngeal mask airway extubation in deeply anesthetized children.

UNLABELLED: The end-tidal anesthetic gas concentration required to prevent the anesthetized patient from coughing or moving during or immediately after the laryngeal mask airway (LMA) extubation is not known. We sought to determine the minimum alveolar concentration of enflurane required for the removal of the LMA in children. We studied 21 nonpremedicated children between 4 and 11 yr of age, ASA physical status I, undergoing procedures below the umbilicus. General anesthesia was induced with a mask by using sevoflurane, nitrous oxide, and oxygen, and the LMA was inserted. Anesthesia was maintained with enflurane, nitrous oxide, and oxygen. At the end of surgery, a predetermined end-tidal enflurane concentration was achieved, and the LMA was removed. Each concentration at which the LMA extubation was attempted was predetermined by the up-and-down method (with 0.1% as a step size). When LMA removal was accomplished without coughing, clenching teeth, or gross purposeful muscular movements during or within 1 min after removal, it was considered a successful LMA removal. Removal was considered to be unsuccessful in patients who developed breath holding or laryngospasm during or immediately after LMA removal. The minimum alveolar concentration of enflurane at which 50% of children had a successful LMA removal was found to be 1.02% (95% CL, 0.95%-1.11%), and the 95% effective dose for successful extubation was 1.14% (95% CL, 1.07%-1.66%). In conclusion, the LMA removal may be accomplished without coughing or moving at 1.02% end-tidal enflurane concentration in 50% of anesthetized children aged 4-11 yr. IMPLICATIONS: There may be fewer problems associated with the laryngeal mask airway extubation when patients are deeply anesthetized. The purpose of this study was to determine the minimum concentration of enflurane for successful removal of the laryngeal mask in children.

The "second gas effect" is not a valid concept.

UNLABELLED: To determine whether the "second gas effect" is valid, we determined the pharmacokinetics of 0.2% enflurane with or without 80% N2) (n = 7 each) under controlled constant volume ventilation in 14 young healthy male patients before their operations. The alveolar (end-tidal) concentration (FA) and inspired concentration (FI) at the mouthpiece and the arterial blood concentration of enflurane were measured, and the ratio of FA to FI was calculated. The FA/FI of enflurane increased rapidly during the first few minutes of administration and then increased slowly. No significant difference was found in the FA/FI between the two groups at any time point (P > 0.05). The arterial blood concentrations of enflurane increased progressively and were not significantly different between the two groups at any time point (P > 0.05). The results indicate that, at high concentrations, N2O neither facilitated the increase of FA nor enhanced the uptake of a companion gas. The second gas effect is a nonexistent phenomenon in clinical practice because the concentrating effect is very weak and the augmentation effect is nonexistent under controlled ventilation. IMPLICATIONS: We studied the effects of N2O on the ratio of alveolar (end-tidal) concentration to inspired concentration of the second gas (enflurane) and on its blood concentration in humans. Nitrous oxide did not affect the alveolar or blood concentration of the second gas under controlled constant volume ventilation. The "second gas effect" is not a valid concept.

[The pharmacokinetic study of desflurane, sevoflurane, isoflurane and enflurane in general anesthesia].

OBJECTIVE: To compare pharmacokinetics of desflurane, sevoflurane, isoflurane and enflurane in general anesthesia. METHODS: 40 patients scheduled for abdominal hysterectomy under general anesthesia were randomly divided into desflurane(D), sevoflurane(S), isofluane(I) and enflurane(E) groups. After induction of anesthesia and endotracheal intubation, desired fraction (Fd) of desflurane(6%), sevoflurane(2%), isoflurane (1.15%) and enflurane(1.7%) in oxygen and nitrous oxide(1:2) were inhaled in D, S, I and E groups, respectively. The fractional end tidal alveolar concentration (Fa) was adjusted to 1MAC during the maintenance of anesthsia. Fa and the fractional inspired concentration of inhaled anesthetics (Fi) were monitored continuously. During operation, fentanyl was infused continuously and pancuronium was injected intermittently. RESULTS: After the beginning of inhalational anesthesia, the time required for Fa/Fi = 1:2 and Fa = 1MAC in D and S groups was significantly shorter than that in E and I groups. The rates of Fa/Fi in D and S groups were significantly higher than those in E and I groups during the maintenance of anesthesia, so were those of Fa/Fd. After cessation of inhalational anesthesia, the time required for Fa equaled to 50% of Fa0(the last Fa during stoping administration of the inhalational anesthesia) in D group was significantly faster than that in the other three groups. CONCLUSIONS: The rates of desflurane wash-in and wash-out are faster than those of other inhaled anesthetics. The depth of anesthesia is easy to control when desflurane is used in general anesthesia.

Repeated enflurane anaesthetics and model predictions: a study of the variability in the predictive performance measures.

We quantified the total variability (reproducibility) and the within-patient but between repeat anaesthetics variability (repeatability) in measures which are used to judge the predictive performance of our physiological model. We studied 14 patients who received enflurane closed-circuit anaesthesia on two occasions. The end-tidal concentrations measured and those predicted served to calculate the predictive performance measures of the model: root mean squared error (rmse = total error), bias (systematic error) and scatter (error around the bias). The overall results were: rmse 15 (7)%, bias 0 (14)% and scatter 9 (3)% (grand mean (total SD)). The within-patient SD values were smaller for the rmse (4%) and bias (10%), but not for scatter (3%). The repeat rmse values and biases were linked to the first results. This implies that these performance measures depended partly on the patient. As there was no association between the personal performance measures and age, sex, body weight, body surface area or body mass index, these characteristics cannot be used to further tune the model.

Factors influencing MAC reduction after cardiopulmonary bypass in dogs.

BACKGROUND: Anaesthetic requirements may be reduced following surgery employing cardiopulmonary bypass (CPB). This study, in dogs, determined the role of a) volatile agents (enflurane [E] vs isoflurane [I]), b) oxygenator (bubble [B] vs membrane [M]), and c) presence [FL] vs absence [NoFL] of an in-line arterial filter in the bypass circuit in altering anaesthetic requirements following CPB. METHODS: Male mongrel dogs were anaesthetized with either enflurane (n = 24) or isoflurane (n = 24). They were randomly assigned to one of eight groups (n = 6 per group); Group 1 (E/B/FL), Group 2 (E/M/FL), Group 3 (E/M/NoFL), Group 4 (E/B/NoFL), Group 5 (I/M/FL), Group 6 (I/B/FL), Group 7 (I/M/NoFL) or Group 8 (I/B/NoFL). MAC was determined using the tail-clamp method at hourly intervals, twice before and three times after a one hour normothermic perfusion using aortoatrial cannulation and CPB. RESULTS: Prior to CPB, MAC was reproducible (enflurane: MAC1 2.17 +/- 0.29 vs MAC2 2.14 +/- 0.28%; isoflurane: MAC1 1.42 +/- 0.31 vs MAC2 1.41 +/- 0.33%) and differed among groups only for the volatile agent employed. Following CPB, MAC was reduced in all groups (P < 0.05 vs pre-CPB measurements) except Group 1 (E/B/FL). The degree of MAC reduction in other groups ranged from 39-64% and was not different based on type of agent employed, use of a membrane or bubble oxygenator, or presence or absence of an in-line arterial filter. CONCLUSION: In dogs, MAC reduction following CPB was variable, not related to type of volatile agent employed, use of a membrane or bubble oxygenator, or presence or absence of an in-line arterial filter. The explanation for reductions in anaesthetic requirements following CPB in this model remains speculative.

Efeitos de monobras e agentes anestésicos no perfil pressórico ocular / The effects of anesthetic agents and maneuvers on the ocular pressure

Justificatica e Objetivos - Diversos trabalhos demonstraram que a variaçäo dos níveis pressóricos oculares dependeram das técnicas ou agentes utilizados. Este estudo visou avaliar os efeitos de manobras e agentes anestésicos diversos incluindo o enflurano e o propofol, no perfil da pressäo ocular. Método - Participaram do estudo trinta pacientes que foram designados a um de três grupos (n=10). Midazolam (0,5 mg.kg elevado a memos um) por via venosa foi administrado na sala de recepçäo anestésica. A anestesia foi induzida com propofol (2,5 mg.kg elevado a menos um) e alfentanil (25 µg.kg elevado a menos um) por via venosa. O grupo A recebeu atracúrio como bloqueador neuromuscular, o grupo B, succinilcolina e o grupo C, salina. A anestesia foi mantida com 66 por cento N2O/O2 enflurano. O olho a ser examinado foi escolhido ao acaso e anestesiado com proparacaína. Os valores de pressäo arterial média, pulso e pressäo ocular foram medidos nos tempos: 1. pré-operatório, antes da administraçäo de midazolam 2. pré-operatório, dez minutos após o midazolam; 3. um minuto após a administraçäo do propofol; 4. após a intubaçäo traqueal; 5. cinco minutos após a intubaçäo traqueal; 6. dez minutos após intubaçäo traqueal; 7. quinze minutos após intubaçäo traqueal. Em uma segunda etapa do estudo, os pacientes do grupo C tiveram o plano anestésico superficializado duas vezes, onde atingiu-se valores de pressäo arterial e freqüência de pulso 35 por cento acima dos valores iniciais. O plano anestésico foi aprofundado com enflurano e propofol. Os valores de pressäo ocular, pressäo arterial média e pulso foram avaliadosnestas circunstâncias...

Context-sensitive half-times and other decrement times of inhaled anesthetics.

UNLABELLED: The length of anesthetic administration influences the rate at which concentrations of anesthetics decrease after their discontinuation. This is true for both intravenous (I.V.) and inhaled anesthetics. This has been explored in detail for I.V. anesthetics using computer simulation to calculate context-sensitive half-times (the time needed for a 50% decrease in anesthetic concentration) and other decrement times (such as the times needed for 80% or 90% decreases in anesthetic concentration). However, decrement times have not been reported for inhaled anesthetics. In this report, published pharmacokinetic parameters and computer simulation were used to compare the context-sensitive half-times and the 80% and 90% decrement times of the expected central nervous system concentrations for enflurane, isoflurane, sevoflurane, and desflurane. The context-sensitive half-times for all four anesthetics are small (<5 min) and do not increase significantly with increasing duration of anesthesia. The 80% decrement times of both sevoflurane and desflurane are also small (<8 min) and do not increase significantly with duration of anesthesia. However, the 80% decrement times of isoflurane and enflurane increase significantly after approximately 60 min of anesthesia, reaching plateaus of approximately 30 and 35 min. The 90% decrement time of desflurane increased slightly from 5 min after 30 min of anesthesia to 14 min after 6 h of anesthesia. It remained significantly less than the 90% decrement times of sevoflurane, isoflurane, and enflurane, which reached values of 65 min, 86 min, and 100 min, respectively, after 6 h of anesthesia. IMPLICATIONS: The major differences in the rates at which desflurane, sevoflurane, isoflurane, and enflurane are eliminated occur in the final 20% of the elimination process.

Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: association between protein acylation and hepatic injury.

In susceptible patients, halothane, enflurane, isoflurane, and desflurane can produce severe hepatic injury by an immune response directed against reactive anesthetic metabolites covalently bound to hepatic proteins. The incidence of hepatotoxicity appears to directly correlate with anesthetic metabolism catalyzed by cytochrome P450 2E1 to trifluoroacetylated hepatic proteins. In the present study, we examined whether the extent of acylation of hepatic proteins in rats by halothane, enflurane, isoflurane, and desflurane correlated with reported relative rates of metabolism. After pretreatment with the P450 2E1 inducer isoniazid, five groups of 10 rats breathed 1.25 minimum alveolar anesthetic concentration (MAC) of halothane, enflurane, isoflurane, or desflurane in oxygen, or oxygen alone, each for 8 h. Immunochemical analysis of livers harvested 18 h after anesthetic exposure showed tissue acylation (greatest to least) after exposure to halothane, enflurane, or isoflurane. Reactivity was not different between isoflurane as compared to desflurane or oxygen alone. An enzyme-linked immunosorbent assay showed halothane reactivity was significantly greater than that of enflurane, isoflurane, desflurane, or oxygen, and that enflurane reactivity was significantly greater than desflurane or oxygen. Sera from patients with a clinical diagnosis of halothane hepatitis showed antibody reactivity against hepatic proteins from rats exposed to halothane or enflurane. No reactivity was detected in rats exposed to isoflurane, desflurane, or oxygen alone. These results indicate that production of acylated proteins may be an important mediator of anesthetic-induced hepatotoxicity.

Minimum alveolar concentration of halothane and enflurane are decreased in early pregnancy.

BACKGROUND: Minimum alveolar concentration (MAC) of isoflurane is decreased in early pregnancy but it is not known whether this occurs to the same extent with other inhalational anesthetics. The MAC of halothane and enflurane were compared in pregnant women undergoing elective termination of pregnancy and in nonpregnant women. METHODS: We studied 16 pregnant women scheduled for termination of pregnancy at 8 to 13 weeks gestation and 16 non-pregnant patients undergoing laparoscopic sterilization. Eight patients in each group received halothane and the others received enflurane. After inhalational induction of anesthesia and tracheal intubation, MAC was determined in each patient by observing the motor response to a 10-s, 50-Hz, 80-mA transcutaneous electric tetanic stimulus to the ulnar nerve at varying concentrations of either halothane or enflurane. The end-tidal concentration of inhalational anesthetic was kept constant for at least 15 min before each stimulus and the concentration was varied ultimately in steps of 0.05 vol% (halothane) or 0.10 vol% (enflurane) until a sequence of three alternate responses (move, not move, move) or (not move, move, not move) was obtained. Minimum alveolar concentration for each person was taken as the mean of the two concentrations just permitting and just preventing movement, and MAC for the group was the median of individual MAC values. Confidence intervals were calculated for the percentage decrease in MAC for pregnant women compared with nonpregnant women. RESULTS: The median (range) MAC of halothane, 0.58 vol% (0.53 to 0.58), and enflurane, 1.15 vol% (0.95-1.25), in the pregnant women were less than those in the nonpregnant women, 0.75 vol% (0.70 to 0.78), P = 0.0005 and 1.65 vol% (1.45 to 1.75), P = 0.0007, respectively. The percentage decrease (95% CI) in MAC for pregnant women was 27% (20 to 27%) for halothane and 30% (24 to 36%) for enflurane. CONCLUSIONS: The MAC of halothane and enflurane were reduced by a similar degree in pregnant women at 8 to 13 weeks gestation compared with nonpregnant women.

The relationship between anaesthetic uptake and cardiac output.

The hypothesis that anaesthetic uptake during maintenance of anaesthesia is related to cardiac output was tested on 21 patients undergoing cardiac surgery. Using a computer-controlled closed breathing system, enflurane was administered to maintain an end-expired concentration of 1%. Cardiac output was measured by thermodilution using a pulmonary artery catheter. A clear qualitative but not quantitative relationship was demonstrated. Changes in anaesthetic requirements at a constant end-expired concentration are a better guide to changes in cardiac output than changes in end-expired carbon dioxide with constant ventilation in patients undergoing cardiac surgery.