Desflurane increases pulmonary alveolar-capillary membrane permeability after aortic occlusion-reperfusion in rabbits: evidence of oxidant-mediated lung injury

BACKGROUND: Pulmonary injury occurs after vascular surgery, with xanthine oxidase (an oxidant generator) released from reperfusing liver and intestines mediating a significant component of this injury. Because halogenated anesthetics have been observed to enhance oxidant-mediated injury in vitro, the authors hypothesized that desflurane would increase alveolar-capillary membrane permeability mediated by circulating xanthine oxidase after thoracic occlusion and reperfusion. METHODS: Rabbits were assigned to one of five groups: aorta occlusion groups administered desflurane (n=14), desflurane and tungstate (xanthine oxidase inactivator, n=12), fentanyl plus droperidol (n=13), and two sham-operated groups (desflurane, n=7 and fentanyl plus droperidol, n=7). Aortic occlusion was maintained for 45 min with a balloon catheter, followed by 3 h of reperfusion. Alveolar-capillary membrane permeability was assessed by measurement of bronchoalveolar lavage fluid protein. Xanthine oxidase activity was determined in plasma and lung tissue. Ascorbic acid content (an antioxidant) was determined in lung tissue. RESULTS: Desflurane was associated with significantly increased alveolar-capillary membrane permeability after aortic occlusion-reperfusion when compared with the fentanyl plus droperidol anesthesia or sham-operated groups (P < 0.05). Inactivation of xanthine oxidase abrogated the alveolar-capillary membrane compromise associated with desflurane. Although significantly greater than for sham-operated animals, plasma xanthine oxidase activities released after aortic occlusion-reperfusion were not different between the two anesthetics. There were no anesthetic-associated differences in lung tissue xanthine oxidase activity. However, desflurane anesthesia resulted in a significant reduction in lung ascorbic acid after aortic occlusion-reperfusion compared with the sham-operated animals. CONCLUSIONS: Desflurane anesthesia increased xanthine oxidase-dependent alveolar-capillary membrane compromise after aortic occlusion-reperfusion in concert with depletion of a key tissue antioxidant.     

Immunohistochemical localization of cytosolic sialidase in the epithelium of rat cornea and conjunctiva

OBJECTIVE: To compare the hemodynamic change, course of recovery and adverse reaction in desflurane, sevoflurane and enflurane inhalation under low flow for patients undergoing selective abdominal surgery. METHODS: Following thiopental induction, 42 patients were divided into three groups: the first group received desflurane, the second sevoflurane and the third enflurane. During surgery, one of the agents around 1 minimum alveolar concentration (MAC) was used for maintenance, with fresh gas flow of 0.3-0.5 L/min for either desflurane or enflurane, and (0.8-1.0) L/min for sevoflurane. Heart rate (HR), blood pressure and end-tidal anesthetic concentration were monitored continuously. Time intervals from cutting off anesthetic to patient opening eyes, following commands, stating the time and location and recalling date of birth were all recorded. In addition, postoperative nausea or vomiting was traced. RESULTS: Desflurane caused the least cardiovascular depression. with mean arterial pressure (MAP) maintained significantly better at 10, 30 and 60 minutes of surgery and with HR stabilized right after incision as well. Its emergence was 2 times faster than sevoflurane, and 5-6 times quicker than enflurane. However, nausea or vomiting was found the lowest in patients receiving sevoflurane, though no distinct difference was shown between desflurane and enflurane. Nevertheless, patients under desflurane suffered less. CONCLUSIONS: Desflurane offers significant advantages for clinical anesthesia maintenance over sevoflurane and enflurane. It provides minimal cardiovascular depression, much quicker recovery, yet still causes some nausea during emergence.     

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

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.     

Changing from isoflurane to desflurane toward the end of anesthesia does not accelerate recovery in humans

BACKGROUND: In an attempt to combine the advantage of the lower solubilities of new inhaled anesthetics with the lesser cost of older anesthetics, some clinicians substitute the former for the latter toward the end of anesthesia. The authors tried to determine whether substituting desflurane for isoflurane in the last 30 min of a 120-min anesthetic would accelerate recovery. METHODS: Five volunteers were anesthetized three times for 2 h using a fresh gas inflow of 2 l/min: 1.25 minimum alveolar concentration (MAC) desflurane, 1.25 MAC isoflurane, and 1.25 MAC isoflurane for 90 min followed by 30 min of desflurane concentrations sufficient to achieve a total of 1.25 MAC equivalent ("crossover"). Recovery from anesthesia was assessed by the time to respond to commands, by orientation, and by tests of cognitive function. RESULTS: Compared with isoflurane, the crossover technique did not accelerate early or late recovery (P > 0.05). Recovery from isoflurane or the crossover anesthetic was significantly longer than after desflurane (P < 0.05). Times to response to commands for isoflurane, the crossover anesthetic, and desflurane were 23 +/- 5 min (mean +/- SD), 21 +/- 5 min, and 11 +/- 1 min, respectively, and to orientation the times were 27 +/- 7 min, 25 +/- 5 min, and 13 +/- 2 min, respectively. Cognitive test performance returned to reference values 15-30 min sooner after desflurane than after isoflurane or the crossover anesthetic. Isoflurane cognitive test performance did not differ from that with the crossover anesthetic at any time. CONCLUSIONS: Substituting desflurane for isoflurane during the latter part of anesthesia does not improve recovery, in part because partial rebreathing through a semiclosed circuit limits elimination of isoflurane during the crossover period. Although higher fresh gas flow during the crossover period would speed isoflurane elimination, the amount of desflurane used and, therefore, the cost would increase.     

Cellular and molecular mechanisms of radiation inhibition of restenosis. Part I: role of the macrophage and platelet-derived growth factor

BACKGROUND: Desflurane, enflurane and isoflurane can be degraded to carbon monoxide (CO) by carbon dioxide absorbents, whereas sevoflurane and halothane form negligible amounts of CO. Carbon monoxide formation is greater with drier absorbent, and with barium hydroxide, than with soda lime. The mechanism, role of absorbent composition and water, and anesthetic structures determining CO formation are unknown. This investigation examined sequential steps in anesthetic degradation to CO. METHODS: Carbon monoxide formation from anesthetics and desiccated barium hydroxide lime or soda lime was determined at equimole and equiMAC concentrations. Carbon monoxide formation from deuterium-substituted anesthetics was also quantified. Proton abstraction from anesthetics by strong base was determined by deuterium isotope exchange. A reactive chemical intermediate was trapped and identified by gas chromatography-mass spectrometry. The source of the oxygen in CO was identified by 18O incorporation. RESULTS: Desflurane,enflurane,andisoflurane(difluoromethylethyl ethers), but not sevoflurane (monofluoromethyl ether), methoxyflurane (methy-ethyl ether), or halothane (alkane) were degraded to CO. The amount of CO formed was desflurane > or = enflurane > isoflurane at equiMAC and enflurane > desflurane > isoflurane at equimole concentrations. Proton abstraction from the difluoromethoxy carbon was greater with potassium than with sodium hydroxide, but unmeasurable with barium hydroxide. Carbon monoxide formation was correlated (r = 0.95-1.00) with difluoromethoxy (enflurane > desflurane > isoflurane > or = methoxyflurane = sevoflurane = 0) but not ethyl carbon proton abstraction. Deuterium substitution on enflurane and desflurane diminished CO formation. Chemical trapping showed formation of a difluorocarbene intermediate from enflurane and desflurane. Incorporation of H2(18)O in barium hydroxide lime resulted in C18O formation from unlabeled enflurane and desflurane. CONCLUSIONS: A difluoromethoxy group is a structural requirement for haloether degradation to CO. Results are consistent with initial base-catalyzed difluoromethoxy proton abstraction (potassium > sodium hydroxide, thus greater CO formation with barium hydroxide lime vs. soda lime) forming a carbanion (reprotonated by water to regenerate the anesthetic, hence requirements for relatively dry absorbent), carbanion decomposition to a difluorocarbene, and subsequent difluorocarbene reaction to form CO.     

Respiratory effects of desflurane anesthesia on spontaneous ventilation in infants and children

Volatile anesthetics depress spontaneous ventilation in a dose-dependent manner with variations in effects among different drugs. The goal of this prospective study was to assess respiratory changes during spontaneous ventilation using desflurane/O2/N2O anesthesia in two groups of children. Both groups were undergoing minor surgery and consisted of children < 2 yr old (Group I) and children > 2 yr old (Group II). They were examined at 0.5, 1, and 1.5 minimum alveolar anesthetic concentration desflurane anesthesia. Induction of anesthesia was performed via a face mask and a mixture of O2/N2O (40:60) with halothane. At lease 20 min after stopping halothane, the respiratory variables were recorded on desflurane anesthesia. Tidal volume and minute ventilation decreased significantly (P <0.05) as desflurane increased from 0.5 to 1.5 MAC in both groups. At 1.5 MAC, the respiratory rate was greater in Group II than in Group I (P <0.05). In both groups, the increase in end-tidal CO2 was significant at 1.5 MAC versus 1 and 0.5 MAC (P <0.05). Apnea, i.e., no respiratory movement for 20 s, occurred at 1.5 MAC in one patient in each group. The respiratory duty cycle did not change in any of the groups. Both indices of paradoxical respiration--amplitude index and delay index--did not change. IMPLICATIONS: Desflurane induces respiratory depression at concentrations higher than 1 minimum alveolar anesthetic concentration mainly due to a decrease in tidal volume. Therefore, desflurane at high concentrations should be used cautiously in infants and children with spontaneous ventilation.     

Delayed onset of malignant hyperthermia induced by isoflurane and desflurane compared with halothane in susceptible swine

BACKGROUND: Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether) is a new inhalational anesthetic currently under investigation for use in humans. Recently, the authors showed that desflurane is a trigger of malignant hyperthermia (MH) in susceptible swine. To date, there has been no in vivo comparison of the relative ability of inhalational anesthetics to trigger MH. The effects of desflurane, isoflurane, and halothane on six MH-susceptible purebred and six MH-susceptible mixed-bred Pietrain swine were examined. METHODS: The animals were exposed to 1 MAC and 2 MAC (if MH was not triggered after 1 MAC hour) doses of each of the three volatile anesthetics in random sequence at 7-10-day intervals and changes in end-tidal CO2, arterial blood gases, serum lactate, core and muscle temperature, blood pressure, and heart rate were measured. RESULTS: There was a statistical difference between anesthetics in the time required to trigger MH; halothane exposure resulted in the fastest onset of an MH episode (20 +/- 5 min), compared with isoflurane (48 +/- 24 min) and desflurane (65 +/- 28 min), both of which required significantly longer exposures. There was no statistical difference between the MH purebred and mixed-bred swine in the time required to trigger MH (defined as a PaCO2 of 70 mmHg) with a given agent, and time to triggering was also independent of the order of exposure to the three anesthetics. Malignant hyperthermia susceptibility was confirmed in ten surviving animals, by both in vivo succinylcholine challenge and in vitro contracture testing. CONCLUSIONS: Although all three volatile anesthetics triggered MH, exposure to halothane resulted in significantly shorter times to MH triggering when compared with desflurane and isoflurane.     

Relationship between anhedonia, affective dependency and autonomy in health subjects

OBJECTIVE: Medical mass spectrometers are configured to detect and measure specific respiratory and anesthetic gases. Unrecognized gases entering these systems may cause erroneous readings. We determined how the Advantage 1100 (Perkin-Elmer, now Marquette Gas Systems, Milwaukee, WI) and PPG-SARA (PPG Biomedical Systems, Lenexa, KS) systems that were not configured to measure desflurane or sevoflurane respond to increasing concentrations of these new potent volatile anesthetic agents. METHODS: Desflurane 0% to 18% in 3% increments or sevoflurane 0% to 7% in 1% increments in 5-L/min oxygen was delivered to the Advantage and PPG-SARA mass spectrometry systems. For each concentration of each agent, the displayed gas analysis readings and uncompensated collector plate voltages were recorded. RESULTS: The Advantage 1100 system read both desflurane and sevoflurane mainly as enflurane and, to a lesser extent, as carbon dioxide and isoflurane. For enflurane(E) readings < 9.9%, the approximate relationships are: %Desflurane = 1.6E; %Sevoflurane = 0.3E. These formulas do not apply if E > 9.9% because of saturation of the summation bus. PPG-SARA read desflurane mainly as isoflurane(I) and, to a lesser extent, as nitrous oxide. PPG-SARA read sevoflurane mainly as enflurane(E) and, to a lesser extent, as nitrous oxide and halothane. The approximate relationships are: %Desflurane = 1.11 (for I < 9%); %Sevoflurane = 2.1E. CONCLUSIONS: Advantage 1100 and PPG-SARA systems not configured for desflurane or sevoflurane display erroneous anesthetic agent readings when these new agents are sampled. Advantage 1100 also displays falsely elevated carbon dioxide readings when desflurane is sampled.     

Economic considerations of the use of new anesthetics: a comparison of propofol, sevoflurane, desflurane, and isoflurane

Cost control in anesthesia is no longer an option; it is a necessity. New anesthetics have entered the market, but economic differences in comparison to standard anesthetic regimens are not exactly known. Eighty patients undergoing either subtotal thyroidectomy or laparoscopic cholecystectomy were randomly divided into four groups, with 20 patients in each group. Group 1 received propofol 1%/sufentanil, Group 2 received desflurane/sufentanil, Group 3 received sevoflurane/sufentanil, and Group 4 received isoflurane/sufentanil (standard anesthesia) for anesthesia. A fresh gas flow of 1.5-2 L/min and 60% N2O in oxygen was used for maintenance of anesthesia, and atracurium was given for muscle relaxation. Concentrations of volatile anesthetics, propofol, and sufentanil were varied according to the patient's perceived need. Isoflurane, desflurane, and sevoflurane consumption was measured by weighing the vaporizers with a precision weighing machine. Biometric data, time of surgery, and time of anesthesia were similar in the four groups. Times for extubation and stay in the postanesthesia care unit (PACU) were significantly longer in the isoflurane group. Use of sufentanil and atracurium did not differ among the groups. Propofol patients required fewer additional drugs in the PACU (e.g., antiemetics), and thus showed the lowest additional costs in the PACU. Total (intra- and postoperative) costs were significantly higher in the propofol group ($30.73 per patient; $0.24 per minute of anesthesia). The costs among the inhalational groups did not differ significantly (approximately $0.15 per minute of anesthesia). We conclude that in today's climate of cost savings, a comprehensive pharmacoeconomic approach is needed. Although propofol-based anesthesia was associated with the highest cost, it is doubtful whether the choice of anesthetic regimen will lower the costs of an anesthesia department. IMPLICATIONS: Cost analysis of anesthetic techniques is necessary in today's economic climate. Consumption of the new inhaled drugs sevoflurane and desflurane was measured in comparison to a standard anesthetic regimen using isoflurane and an IV technique using propofol. Propofol-based anesthesia was associated with the highest costs, whereas the costs of the new inhaled anesthetics sevoflurane and desflurane did not differ from those of a standard, isoflurane-based anesthesia regimen.     

Waste gas exposure during desflurane and isoflurane anaesthesia

BACKGROUND: Currently, there are no data available concerning the occupational exposure to desflurane during general anaesthesia. This prospective, randomized study reports on occupational exposure to desflurane, compared to isoflurane, in a modern operation theatre (OT). METHODS: The study was performed in an OT equipped with a modern air-conditioning system and with a low-leakage anaesthesia machine connected to a central scavenging system. Trace concentrations of the anaesthetics were measured continuously by means of a photoacoustic infrared spectrometer during general anaesthesia in 30 patients undergoing eye surgery. Values were obtained within the breathing zone of the anaesthetist, the surgeon, the auxiliary nurse and at the mouth of the patient. RESULTS: Desflurane and isoflurane were administered with median (range) endtidal concentrations of 4.7 (3.8-10.3) vol% and 0.9 (0.6-1.4) vol%, respectively. The personnel-related median values of the average trace concentrations of desflurane and isoflurane were 0.5 (0.01-7.5) ppm and 0.2 (0.01-1.6) ppm, respectively. CONCLUSIONS: Occupational exposure to desflurane is low in the environment of a modern OT, even though it has to be administered in approximately 5-fold higher concentrations compared to isoflurane.     

The effects of sevoflurane, isoflurane, halothane, and enflurane on hemodynamic responses during an inhaled induction of anesthesia via a mask in humans

A rapid increase in isoflurane or desflurane concentration induces tachycardia and hypertension and increases-plasma catecholamine concentration. Little information is available as to whether sevoflurane, halothane, and enflurane induce similar responses during anesthesia induction via mask. Fifty ASA physical status I patients, aged 20-40 yr, and scheduled for elective minor surgery, received one of four volatile anesthetics: sevoflurane, isoflurane, halothane, or enflurane. Anesthesia was induced with thiamylal, followed by inhalation of 0.9 minimum alveolar anesthetic concentration (MAC) of the anesthetic in 100% oxygen via mask. The inspired concentration of anesthetic was increased by 0.9 MAC every 5 min to a maximum of 2.7 MAC. Heart rate (HR) and systolic blood pressure (SBP) were measured before and every minute for 15 min during anesthetic inhalation. In the sevoflurane and isoflurane groups, venous blood samples were drawn to determine the concentrations of plasma epinephrine and norepinephrine 3 min after each increase in anesthetic concentration. Sustained increments in HR were observed after increases in inspired isoflurane concentration to 1.8 MAC and 2.7 MAC (peak changes of 15 +/- 3 and 17 +/- 3 bpm, respectively). Isoflurane also increased SBP transiently after the inspired concentration was increased to 2.7 MAC (peak change of 10 +/- 4 mm Hg). Enflurane increased HR after the inspired concentration was increased to 2.7 MAC (peak change of 9 +/- 2 bpm). In contrast, changes in sevoflurane and halothane concentrations did not induce hyperdynamic responses. Plasma norepinephrine concentration in the isoflurane group was significantly higher than that in the sevoflurane group during 2.7 MAC (P = 0.022). We propose that there is a direct relationship between airway irritation of the anesthetic and immediate cardiovascular change during an inhaled induction of anesthesia.     

Whole-body kinetics and dosimetry of L-3--123I-iodo-alpha-methyltyrosine

BACKGROUND: Desflurane anesthesia can produce cerebral metabolic depression and increase cerebral blood flow. We evaluated the effect of desflurane on brain tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2) and pH during neurosurgery. METHODS: Following a craniotomy, the dura was opened and a Paratrend 7 sensor, which measures PO2, PCO2, pH and temperature, was inserted into brain tissue. In 6 control patients in group 1, anesthesia was maintained constant with 3% end-tidal desflurane over 60 min, including a 30-min stabilization period. In group 2, 9 patients were ventilated with 3% desflurane under baseline conditions. After a 30-min stabilization period, baseline tissue gases and pH were measured and end-tidal desflurane was increased to 6% and then 9% for 15-min intervals. Mean arterial pressure (MAP) was maintained with intravenous phenylephrine. RESULTS: Under baseline conditions, cardiovascular and brain tissue measures were similar between the 2 groups. Increasing end-tidal desflurane from 3% to 9% produced burst-suppression EEG in all patients and significantly increased tissue PO2 and pH and decreased PCO2. No parameters changed significantly in the control group during steady-state anesthesia. CONCLUSION: These results show that 9% desflurane can improve brain tissue metabolic status before temporary brain artery occlusion if cerebral perfusion pressure is maintained. This may be particularly important in patients with symptoms of ischemia before surgery.     

Desflurane and isoflurane exert modest beneficial actions on left ventricular diastolic function during myocardial ischemia in dogs

BACKGROUND: Volatile anesthetics exert cardioprotective effects during myocardial ischemia. This investigation examined the regional systolic and diastolic mechanical responses to brief left anterior descending coronary artery (LAD) occlusion in the central ischemic zone and in remote normal myocardium in the conscious state and during desflurane and isoflurane anesthesia. METHODS: Eighteen experiments were performed in nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, cardiac output, LAD coronary blood flow velocity, and LAD and left circumflex coronary artery subendocardial segment length. Regional myocardial contractility was evaluated with the slope of the preload recruitable stroke work relationship determined from a series of left ventricular pressure-segment length diagrams in the LAD and left circumflex coronary artery zones. Diastolic function was assessed with a time constant of isovolumic relaxation (tau), maximum segment lengthening velocity in LAD and left circumflex coronary artery regions, and regional chamber stiffness constants derived using monoexponential and three-element exponential curve fitting in each zone. On separate experimental days, hemodynamics and indices of regional functional were obtained in the conscious state and during 1.1 and 1.6 minimum alveolar concentration end-tidal desflurane or isoflurane before and during LAD occlusion. RESULTS: In conscious dogs, LAD occlusion abolished regional stroke work, increased chamber stiffness (monoexponential: 0.39 +/- 0.04 during control to 1.34 +/- 0.39 mm-1 during LAD occlusion), and decreased the rate of early ventricular filling in the ischemic zone. These changes were accompanied by increased contractility (slope: 103 +/- 8 during control to 112 +/- 7 mmHg during LAD occlusion), rapid filling rate (maximum segment lengthening velocity: 46 +/- 5 during control to 55 +/- 7 mm.s-1 during LAD occlusion), and chamber stiffness (monoexponential: 0.43 +/- 0.05 during control to 1.14 +/- 0.25 mm-1 during LAD occlusion) in the normal region. Increases in tau were also observed in the conscious state during the period of myocardial ischemia. Desflurane and isoflurane increased tau and decreased the slope and maximum segment lengthening velocity in a dose-related manner. Monoexponential and three-element element exponential curve fitting were unchanged by the volatile anesthetics in the absence of ischemia. Myocardial contractility and rapid filling rate were enhanced in the nonischemic region during LAD occlusion in the presence of desflurane and isoflurane. In contrast to the findings in the conscious state, ischemia-induced increases in tau and chamber stiffness in the ischemic and normal zones were attenuated during anesthesia induced by desflurane and isoflurane. CONCLUSIONS: The results indicate that increases in contractility of remote myocardium during brief regional ischemia were preserved in the presence of desflurane and isoflurane anesthesia. In addition, desflurane and isoflurane blunted ischemia-induced increases in tau and regional chamber stiffness in both the ischemic and nonischemic zones. These results demonstrate that the volatile anesthetics may exert important beneficial actions on left ventricular mechanics in the presence of severe abnormalities in systolic and diastolic function during ischemia.     

Time-dependent changes in heart rate and pupil size during desflurane or sevoflurane anesthesia

To better characterize alterations in autonomic function associated with prolonged anesthesia, we tested the hypothesis that the time-dependent effects of sevoflurane and desflurane differ. We studied seven male volunteers, each anesthetized for 8 h with 1.25 minimum alveolar anesthetic concentration desflurane on one study day and with 8 h sevoflurane on another. These volunteers did not undergo surgery and were minimally stimulated during the study. Measurements included blood pressure, heart rate, pupillary size and light reactivity, concentrations of serum catecholamines, and carbon dioxide production. Over time, heart rate and pupil size increased significantly. During 6 of the 14 anesthetics (45%), heart rate at some point exceeded 95 bpm; similarly, pupil size at some time exceeded 5 mm during 8 anesthetics (57%). In contrast, plasma catecholamine concentrations and carbon dioxide production remained unchanged, and blood pressure remained nearly constant. There are thus substantial time-dependent changes in autonomic functions during prolonged anesthesia, even in unstimulated, nonsurgical volunteers, but we could not detect a difference in these changes during desflurane compared with sevoflurane anesthesia. Implications: Pupil size and heart rate changes are used to guide the delivery of anesthesia. In volunteers, pupil size and heart rate increased with increasing duration of constant desflurane or sevoflurane anesthesia. Thus, anesthetic duration alters heart rate and pupil size independent of surgery and changes in anesthetic delivery.     

Emergence of elderly patients from prolonged desflurane, isoflurane, or propofol anesthesia

Recovery from prolonged anesthesia might be compromised in elderly patients. Desflurane (DES) may be particularly well suited to achieve a rapid postoperative recovery because of its low lipid solubility. Postoperative recovery was compared in 45 elderly patients randomized to receive either DES, isoflurane (ISO), or propofol (PRO) to maintain anesthesia. Anesthesia was induced with PRO, vecuronium, and fentanyl and maintained with N2O, fentanyl, and the study drug. Times from end of anesthesia to tracheal extubation, eye opening and hand squeezing on command, and ability to state name and date of birth were recorded. Sedation and psychometric evaluation were tested 0.5, 1, 1.5, 2, and 24 h postoperatively. Results are given as means +/- SD. Differences among were analyzed by chi2 or analysis of variance. P < 0.05 compared with DES was considered significant. After a prolonged anesthesia (199 +/- 57 min with DES), immediate recovery times were significantly shorter with DES than with ISO or PRO (times to eye opening: 5.6 +/- 3.4 min, 11.5 +/- 8.4 min, and 11.9 +/- 7.6 min; times to extubation: 6.9 +/- 3 min, 13.1 +/- 8.9 min, 9.9 +/- 6.5 min for DES, ISO, and PRO, respectively). Intermediate recovery, as measured by psychometric testing, sedation levels, and time to discharge from the postanesthesia care unit, was similar in the three groups. In this study, DES provided a transient advantage compared with ISO or PRO with respect to early recovery after prolonged general anesthesia in elderly patients. IMPLICATIONS: Recovery from prolonged anesthesia can sometimes be problematic in elderly patients. We evaluated 45 elderly patients who received either desflurane, isoflurane, or propofol for anesthesia. We found that desflurane provided a transient advantage in terms of postoperative recovery, but whether this difference is clinically important remains to be demonstrated.     

Desflurane-mediated sympathetic activation occurs in humans despite preventing hypotension and baroreceptor unloading

BACKGROUND: Increasing concentrations of desflurane result in progressive decreases in blood pressure (BP) and, unlike other currently marketed, potent volatile anesthetics, heightened sympathetic nervous system activity. This study aimed to determine whether baroreflex mechanisms are involved in desflurane-mediated sympathetic excitation. METHODS: Healthy volunteers were anesthetized with desflurane (n = 8) or isoflurane (n = 9). Heart rate (HR; measured by electrocardiograph), blood pressure (BP; measured by arterial catheter), and efferent sympathetic nerve activity (SNA; obtained from percutaneous recordings from the peroneal nerve) were monitored. Baroreflex sensitivity was evaluated at baseline while volunteers were conscious and during 0.5, 1, and 1.5 minimum alveolar concentration (MAC) anesthesia via bolus injections of nitroprusside (100 microg) and phenylephrine (150 microg) to decrease and increase BP. To prevent the BP decline with increasing depths of anesthesia, phenylephrine was infused to maintain mean BP at the 0.5 MAC level. RESULTS: The HR, BP, and SNA were similar between the groups at the conscious baseline measurement. Efferent SNA did not change during higher MAC of isoflurane, but it increased progressively as desflurane concentrations were increased beyond 0.5 MAC, despite maintaining BP at the 0.5 MAC value with phenylephrine infusions (P < 0.05). Cardiac baroslopes (based on changes in HR) were progressively and similarly decreased with increasing concentrations of isoflurane and desflurane (P < 0.05). Sympathetic baroslopes (based on SNA) decreased with increasing isoflurane concentrations but were maintained with increasing concentrations of desflurane; the response was significantly different between groups. CONCLUSIONS: The increase in basal levels of SNA with increasing concentrations of desflurane persisted despite "fixing" BP and thus is probably not due to hypotension and unloading of the baroreceptors. Further, the preservation of reflex increases in SNA to nitroprusside during desflurane indicates that desflurane preserves one component of the baroreflex in humans when BP is "fixed."     

A new tool for studying the molecular architecture of the fungal cell wall: one-step purification of recombinant trichoderma beta-(1-6)-glucanase expressed in Pichia pastoris

We assessed the anesthetic properties of helium and neon at hyperbaric pressures by testing their capacity to decrease anesthetic requirement for desflurane using electrical stimulation of the tail as the anesthetic endpoint (i.e., the minimum alveolar anesthetic concentration [MAC]) in rats. Partial pressures of helium or neon near those predicted to produce anesthesia by the Meyer-Overton hypothesis (approximately 80-90 atm), tended to increase desflurane MAC, and these partial pressures of helium and neon produced convulsions when administered alone. In contrast, the noble gases argon, krypton, and xenon were anesthetic with mean MAC values of (+/- SD) of 27.0 +/- 2.6, 7.31 +/- 0.54, and 1.61 +/- 0.17 atm, respectively. Because the lethal partial pressures of nitrogen and sulfur hexafluoride overlapped their anesthetic partial pressures, MAC values were determined for these gases by additivity studies with desflurane. Nitrogen and sulfur hexafluoride MAC values were estimated to be 110 and 14.6 atm, respectively. Of the gases with anesthetic properties, nitrogen deviated the most from the Meyer-Overton hypothesis. Implications: It has been thought that the high pressures of helium and neon that might be needed to produce anesthesia antagonize their anesthetic properties (pressure reversal of anesthesia). We propose an alternative explanation: like other compounds with a low affinity to water, helium and neon are intrinsically without anesthetic effect.     

Desflurane, sevoflurane, and isoflurane impair canine left ventricular-arterial coupling and mechanical efficiency

BACKGROUND: The effects of desflurane, sevoflurane, and isoflurane on left ventricular-arterial coupling and mechanical efficiency were examined and compared in acutely instrumented dogs. METHODS: Twenty-four open-chest, barbiturate-anesthetized dogs were instrumented for measurement of aortic and left ventricular (LV) pressure (micromanometer-tipped catheter), dP/dtmax, and LV volume (conductance catheter). Myocardial contractility was assessed with the end-systolic pressure-volume relation (Ees) and preload recruitable stroke work (Msw) generated from a series of LV pressure-volume diagrams. Left ventricular-arterial coupling and mechanical efficiency were determined by the ratio of Ees to effective arterial elastance (Ea; the ratio of end-systolic arterial pressure to stroke volume) and the ratio of stroke work (SW) to pressure-volume area (PVA), respectively. RESULTS: Desflurane, sevoflurane, and isoflurane reduced heart rate, mean arterial pressure, and left ventricular systolic pressure. All three anesthetics caused similar decreases in myocardial contractility and left ventricular afterload, as indicated by reductions in Ees, Msw, and dP/dtmax and Ea, respectively. Despite causing simultaneous declines in Ees and Ea, desflurane decreased Ees/Ea (1.02 +/- 0.16 during control to 0.62 +/- 0.14 at 1.2 minimum alveolar concentration) and SW/PVA (0.51 +/- 0.04 during control to 0.43 +/- 0.05 at 1.2 minimum alveolar concentration). Similar results were observed with sevoflurane and isoflurane. CONCLUSIONS: The present findings indicate that volatile anesthetics preserve optimum left ventricular-arterial coupling and efficiency at low anesthetic concentrations (< 0.9 minimum alveolar concentration); however, mechanical matching of energy transfer from the left ventricle to the arterial circulation degenerates at higher end-tidal concentrations. These detrimental alterations in left ventricular-arterial coupling produced by desflurane, sevoflurane, and isoflurane contribute to reductions in overall cardiac performance observed with these agents in vivo.     

Channeling of three newly introduced antidepressants to patients not responding satisfactorily to previous treatment

OBJECTIVE: Trifluoromethane and CO are produced simultaneously during the breakdown of isoflurane and desflurane by dry CO2 absorbents. Trifluoromethane interferes with anesthetic agent monitoring, and the interference can be used as a marker to indicate anesthetic breakdown with CO production. This study tests representative types of gas monitors to determine their ability to provide a clinically useful warning of CO production in circle breathing systems. METHODS: Isoflurane and desflurane were reacted with dry Baralyme at 45 degrees C. Standardized samples of breakdown products were created from mixtures of reacted and unreacted gases to simulate the partial degrees of reaction which might result during clinical episodes of anesthetic breakdown using 1% or 2% isoflurane and 6% or 12% desflurane. These mixtures were measured by the monitors tested, and the indication of the wrong agent or a mixture of agents due to the presence of trifluoromethane was recorded and related to the CO concentration in the gas mixtures. RESULTS: When presented with trifluoromethane from anesthetic breakdown, monochromatic infrared monitors displayed inappropriately large amounts of isoflurane or desflurane. Agent identifying infrared and Raman scattering monitors varied in their sensitivity to trifluoromethane. Mass spectrometers measuring enflurane at mass to charge = 69 were most sensitive to trifluoromethane. CONCLUSION: Monochromatic infrared monitors were unable to indicate anesthetic breakdown via interference by trifluoromethane, but did indicate falsely elevated anesthetic concentrations. Agent identifying infrared and Raman monitors provided warning of desflurane breakdown via the interference of trifluoromethane by displaying the wrong agent or mixed agents, but may not be sensitive enough to warn of isoflurane breakdown Some mass spectrometers provided the most sensitive warnings to anesthetic breakdown via trifluoromethane, but additional data processing by some patients monitor units reduced their overall effectiveness.     

Cross-linked DNA duplexes--exonuclease stability and interaction with the nucleic transcription factor of the kappa light-chain enhancer (NF-kappaB)

This study documents the differences in kinetics of 2 h (n = 7) and 4 h (n = 9) of 1.25 minimum alveolar anesthetic concentration (MAC) of desflurane (9.0%) versus (on a separate occasion) sevoflurane (3.0%), both administered in a fresh gas inflow of 2 L/min. These data are extensions of our previous 8-h (n = 7) studies of these anesthetics. By 10 min of anesthetic administration, average inspired (F(I)) and end-tidal concentration (F(A)) (F(I)/F(A); the inverse of the more commonly used F(A)/F(I)) decreased to less than 1.15 for both anesthetics, with the difference from 1.0 nearly twice as great for sevoflurane as for desflurane. During all sevoflurane administrations, F(A)/F(I) for Compound A [CH2F-O-C(=CF2) (CF3); a vinyl ether resulting from the degradation of sevoflurane by Baralyme] equaled approximately 0.8, and the average inspired concentration equaled approximately 40 ppm. Compound A is of interest because at approximately 150 ppm-h, it can induce biochemical and histological evidence of glomerular and tubular injury in rats and humans. During elimination, F(A)/F(A0) for Compound A (F(A0) is the last end-tidal concentration during anesthetic administration) decreased abruptly to 0 after 2 h and 4 h of anesthesia and to approximately 0.1 (F(A) approximately 3 ppm) after 8 h of anesthesia. In contrast, F(A)/F(A0) for desflurane and sevoflurane decreased in a conventional, multiexponential manner, the decrease being increasingly delayed with increasing duration of anesthetic administration. F(A)/F(A0) for sevoflurane exceeded that for desflurane for any given duration of anesthesia, and objective and subjective measures indicated a faster recovery with desflurane. Times (mean +/- SD) to initial response to command (2 h 10.9 +/- 1.2 vs 17.8 +/- 5.1 min, 4 h 11.3 +/- 2.1 vs 20.8 +/- 4.8 min, 8 h 14 +/- 4 vs 28 +/- 8 min) and orientation (2 h 12.7 +/- 1.6 vs 21.2 +/- 4.6 min, 4 h 14.8 +/- 3.1 vs 25.3 +/- 6.5 min, 8 h 19 +/- 4 vs 33 +/- 9 min) were shorter with desflurane. Recovery as defined by the digit symbol substitution test, P-deletion test, and Trieger test results was more rapid with desflurane. The incidence of vomiting was greater with sevoflurane after 8 h of anesthesia but not after shorter durations. We conclude that for each anesthetic duration, F(I) more closely approximates F(A) with desflurane during anesthetic administration, F(A)/F(A0) decreases more rapidly after anesthesia with desflurane, and objective measures indicate more rapid recovery with desflurane. Finally, it seems that after 2-h and 4-h administrations, all Compound A taken up is bound within the body. Implications: Regardless of the duration of anesthesia, elimination is faster and recovery is quicker for the inhaled anesthetic desflurane than for the inhaled anesthetic sevoflurane. The toxic degradation product of sevoflurane, Compound A, seems to bind irreversibly to proteins in the body.