Simple strategy for sequencing cDNA clones

This randomized, open-label study compared the investigational inhalational anesthetic sevoflurane with isoflurane in 47 healthy women undergoing elective ambulatory surgery. The women were randomized to receive either sevoflurane or isoflurane in 60% nitrous oxide-oxygen. Induction with thiopental 3-6 mg/kg was followed by vecuronium 0.1 mg/kg and fentanyl 0-200 micrograms. Duration of anesthesia, time to emergence, orientation, length of stay in the surgical unit, and hospital discharge were recorded. The emergence, length of stay, and discharge times after discontinuation of sevoflurane were 9.7 +/- 0.7, 120.6 +/- 8.0, and 244 +/- 15 minutes, respectively, and for isoflurane were 11.9 +/- 1.4, 106.8 +/- 7.1, and 282 +/- 24 minutes, respectively (NS). The isoflurane group had a higher frequency of postoperative cough. At the end of surgery, the sevoflurane group received a deeper level of anesthesia (minimum alveolar concentration 1.5 vs 1.3), however, these patients were oriented earlier (13.6 +/- 1.1 min vs 17.0 +/- 1.5 min isoflurane; p = 0.02) after discontinuation of anesthesia, although this difference is of little clinical significance.     

Renal function in patients during and after hypotensive anesthesia with sevoflurane

STUDY OBJECTIVES: To evaluate renal function during and after hypotensive anesthesia with sevoflurane compared with isoflurane in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Rosai Hospital. PATIENTS: 26 ASA physical status I and II patients scheduled for orthopedic surgery. INTERVENTIONS: Patients received isoflurane, nitrous oxide (N2O), and fentanyl (Group I = isoflurane group; n = 13) or sevoflurane, N2O, and fentanyl (Group S = sevoflurane group; n = 13). Controlled hypotension was induced with either isoflurane or sevoflurane to maintain mean arterial pressure at 60 mmHg for 120 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements included serum inorganic fluoride (previously speculated to influence renal function), creatinine clearance (CCr; to assess renal glomerular function), urinary N-acetyl-beta-D-glucosaminidase (NAG; to assess renal tubular function), blood urea nitrogen (BUN), and serum creatinine (as clinical renal function indices). Serum fluoride, CCr, and NAG were measured before hypotension, 60 minutes, and 120 minutes after the start of hypotension, 30 minutes after recovery of normotension, and on the first postoperative day. BUN and serum creatinine were measured preoperatively and on the third and seventh postoperative days. Minimum alveolar concentration times hour was 3.6 +/- 1.8 in Group I and 4.0 +/- 0.7 in Group S. In both groups, BUN and serum creatinine did not change, and CCr significantly decreased after the start of hypotension. In Group I, serum fluoride and NAG did not change. In Group S, serum fluoride significantly increased after the start of hypotension compared with prehypotension values and compared with Group I values. In addition, NAG significantly increased at 120 minutes after the start of hypotension and at 30 minutes after recovery of normotension, but returned to prehypotension values on the first postoperative day. CONCLUSIONS: Two hours of hypotensive anesthesia with sevoflurane under 5 L/min total gas flow in patients having no preoperative renal dysfunction transiently increased NAG, which is consistent with a temporary, reversible disturbance of renal tubular function.     

Neuromuscular effects of rocuronium during sevoflurane, isoflurane, and intravenous anesthesia

The potency and time course of action of rocuronium were studied in patients anesthetized with 66% nitrous oxide in oxygen and 1.5 minimum alveolar anesthetic concentration of sevoflurane or isoflurane, or a propofol infusion. Potency was estimated by using the single-bolus technique. Neuromuscular block was measured by stimulation of the ulnar nerve and by recording the force of contraction of the adductor pollicis muscle. The mean (95% confidence limits) of the 50% and 95% effective doses were estimated tobe 142 (129-157) and 265 (233-301) microg/ kg, 165 (146-187) and 324 (265-396) microg/kg, and 183 (163-207) and 398 (316-502) microg/kg during sevoflurane, isoflurane, and propofol anesthesia, respectively (P < 0.05 for sevoflurane versus propofol). The mean +/- SD times to onset of maximal block after rocuronium 0.6 mg/kg were 0.96 +/- 0.16, 0.90 +/- 0.16, and 1.02 +/- 0.15 min during sevoflurane, isoflurane, and propofol anesthesia, respectively. The respective times to recovery of the first response in the train-of-four (TOF) stimulation (T1) to 25% and 90% were 45 +/- 13.1 and 83 +/- 29.3 min, 35 +/- 6.1 and 56 +/- 15.9 min, and 35 +/- 9.2 and 55 +/- 19.4 min. The times to recovery of the TOF ratio to 0.8 were 103 +/- 30.7, 69 +/- 20.4, and 62 +/- 21.1 min, and the 25%-75% recovery indices were 26 +/- 11.7, 12 +/- 5.0, and 14 +/- 6.9 min, respectively. There were no differences among groups in the times for onset of action or to recovery of T1 to 25%. However, the times for recovery of T1 to 90%, TOF ratio to 0.8, and recovery index in the sevoflurane group were all significantly longer compared with the other two groups (P < 0.05, < 0.01, and < 0.01, respectively). We conclude that the effects of rocuronium, especially duration of action, are significantly enhanced during sevoflurane compared with isoflurane and propofol anesthesia. IMPLICATIONS: In routine clinical use, the effects of rocuronium are enhanced by sevoflurane, in comparison with isoflurane and propofol anesthesia, and the recovery is slower. Particular attention should be paid to monitoring of neuromuscular block during sevoflurane anesthesia.     

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.     

The motor organization of the sense of rhythm

Serum inorganic fluoride levels in obese versus control patients were compared during and after sevoflurane anesthesia. Mean serum inorganic fluoride levels in the obese group increased more rapidly and were significantly higher than in the control group at each sampling time (P < 0.01). The area under the curve of fluoride concentration, versus time up to 24 h and 48 h in the obese patients, was significantly greater than that in the nonobese patients (P < 0.001). Peak serum fluoride level in the obese patients was 51.7 +/- 2.5 mumol/L and exceeded 50 mumol/L for nearly 2 h. Our study showed that serum fluoride concentrations between mildly obese and nonobese patients differed during and after sevoflurane anesthesia.     

Influence of sevoflurane and isoflurane anesthesia on renal function in elderly patients

We examined the influence of sevoflurane and isoflurane anesthesia on renal function in elderly patient who underwent gastrectomy. Plasma inorganic fluoride level was significantly higher in sevoflurane group compared with isoflurane group from 3 hours after the beginning of anesthesia to the 3rd operative day. In contrast, parameters such as urinary beta 2 microglobulin, urinary N-acetyl-beta-D-glucosaminidase, and urinary gamma-GTP activities increased in both groups, but the increase was not significant. Serum BUN and creatinine levels were within normal limits. These results suggest that elderly patients without renal dysfunction appear unlikely to have any significant problem after prolonged sevoflurane anesthesia.     

Effects of xenon on hemodynamic responses to skin incision in humans

BACKGROUND: The authors evaluated the hemodynamic suppressive effects of xenon in combination with sevoflurane at skin incision in patients undergoing surgery. METHODS: Forty patients were assigned randomly to receive one of the following four anesthetics: 1.3 minimum alveolar concentration (MAC) sevoflurane, 0.7 MAC xenon with 0.6 MAC sevoflurane, 1 MAC xenon with 0.3 MAC sevoflurane, or 0.7 MAC nitrous oxide with 0.6 MAC sevoflurane (n = 10 each group). Systolic blood pressure and heart rate were measured before anesthesia, before incision, and approximately 1 min after incision. RESULTS: The changes in hemodynamic variables in response to incision were less with sevoflurane in combination with xenon and nitrous oxide than with sevoflurane alone. Changes in heart rate (in beats/min) were 19+/-11 (+/- SD) for sevoflurane alone, 11+/-6 for 0.7 MAC xenon-sevoflurane, 4+/-4 for 1 MAC xenon-sevoflurane, and 8+/-7 for nitrous oxide-sevoflurane. Changes in systolic blood pressure were 35+/-18 mmHg for sevoflurane alone, 18+/-8 mmHg for 0.7 MAC xenon-sevoflurane, 16+/-7 mmHg for 1 MAC xenon-sevoflurane, and 14+/-10 mmHg for nitrous oxide-sevoflurane. CONCLUSIONS: Xenon and nitrous oxide in combination with sevoflurane can reduce hemodynamic responses to skin incision compared with sevoflurane alone. One probable explanation may be that xenon has analgesic properties similar to those of nitrous oxide, although the exact mechanism is yet to be determined.     

Preservation of the ration of cerebral blood flow/metabolic rate for oxygen during prolonged anesthesia with isoflurane, sevoflurane, and halothane in humans

BACKGROUND: In several animal studies, an increase in cerebral blood flow (CBF) produced by volatile anesthetics has been reported to resolve over time during prolonged anesthesia. It is important to investigate whether this time-dependent change of CBF takes place in humans, especially in clinical situations where surgery is ongoing under anesthesia. In this study, to evaluate the effect of prolonged exposure to volatile anesthetics (isoflurane, sevoflurane, and halothane), the CBF equivalent (CBF divided by cerebral metabolic rate for oxygen (CMRO2) was determined every 20 min during anesthesia lasting more than 4h in patients. METHODS: Twenty-four surgical patients were assigned to three groups at random to receive isoflurane, sevoflurane, or halothane (8 patients each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5 and 1.0 MAC before surgery and then 1.5 MAC for the 3 h of surgical procedure. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 60 mmHg, using phenylephrine infusion, if necessary. CBF equivalent was calculated every 20 min as the reciprocal of arterial-jugular venous oxygen content difference. RESULTS: CBF equivalent at 0.5 MAC of isoflurane, halothane, and sevoflurane was 21 +/- 4, 20 +/- 3, and 21 +/- 5 ml blood/ml oxygen, respectively. All three examined volatile anesthetics significantly (P<0.01) increased CBF equivalent in a dose-dependent manner (0.5, 1.0, 1.5 MAC). AT 1.5 MAC, the increase of CBF equivalent with all anesthetics was maintained increased with minimal fluctuation for 3 h. The mean value of CBF equivalent at 1.5 MAC in the isoflurane group (45 +/- 8) was significantly (P<0.01) greater than those in the halothane (32 +/- 8) and sevoflurane (31 +/- 8) groups. Electroencephalogram was found to be relatively unchanged during observation periods at 1.5 MAC. CONCLUSIONS: These results demonstrate that CBF/CMRO2 ratio is markedly increased above normal and maintained during prolonged inhalation of volatile anesthetics in humans. It is impossible to determine whether these data indicate a stable CBF or whether CBF and CMRO2 are changing in parallel during the observation period. The unchanging electroencephalographic pattern suggests that the former possibility is more likely and that the increase of CBF produced by volatile anesthetics is maintained over time without decay, which has been reported in several animal studies. It also is suggested that isoflurane possesses greater capability to maintain global CBF relative to CMRO(2) than does halothane or sevoflurane. time.)     

Evidence for regulation of the NADH peroxidase gene (npr) from Enterococcus faecalis by OxyR

To evaluate residual effects of inhalational anesthetics after reversal of neuromuscular blocking agent, neuromuscular function was monitored after halothane or sevoflurane anesthesia in thirty-seven patients (ASA physical status I or II) for elective surgery after obtaining informed consent. Electromyograph of the adductor pollicis muscle in response to train of four (TOF) stimulation was monitored throughout the study. The first twitch of TOF (T1; % of its control) and the ratio of the fourth twitch to the first twitch of TOF (T4/T1; TR) were recorded at 0, 2, 5, 10, and 15 min after reversal. The patients were divided into five groups; 1) the fentanyl group (n = 7) received fentanyl/N2O; 2) in the halothane stop group (n = 6), halothane was discontinued at least fifteen minutes before neostigmine administration; 3) in the halothane stable group (n = 7), 0.7% halothane was maintained until fifteen minutes after neostigmine; 4) in the sevoflurane stop group (n = 12), sevoflurane was discontinued fifteen minutes before the reversal; 5) in the sevoflurane stable group (n = 5), 3% sevoflurane was maintained until fifteen minutes after the reversal. Anesthesia was induced by thiopental 4 mg.kg-1 and suxamethonium 1 mg.kg-1 and the patients were intubated. After initial dose of vecuronium 0.1 mg.kg-1, the additional dose of 0.02 mg.kg-1 was administered to maintain T1 under 10% of the control value. At the end of the surgery atropine 0.015 mg.kg-1 and neostigmine 0.04 mg.kg-1 were administered to reverse vecuronium when T1 had recovered to 25% of its control. Halothane groups did not differ from fentanyl group. Recovery of T1 at 15 min was suppressed after discontinuation of sevoflurane (86.0 +/- 8.2%) in comparison with fentanyl (97.0 +/- 8.3%). Both T1 (75.4 +/- 12.2%) and TR (68.0 +/- 12.6%) at 15 min after the reversal during 3% sevoflurane inhalation were below those of the stable group. We conclude that the residual sevofulrane after discontinuation of inhalation may impair the neuromuscular transmission after the reversal of neuromuscular blockade. Neuromuscular function should be monitored after the end of anesthesia even though the patient is fully awake.     

Epidural anesthesia impairs both central and peripheral thermoregulatory control during general anesthesia

BACKGROUND: The authors tested the hypotheses that: (1) the vasoconstriction threshold during combined epidural/general anesthesia is less than that during general anesthesia alone; and (2) after vasoconstriction, core cooling rates during combined epidural/general anesthesia are greater than those during general anesthesia alone. Vasoconstriction thresholds and heat balance were evaluated under controlled circumstances in volunteers, whereas the clinical importance of intraoperative thermoregulatory vasoconstriction was evaluated in patients. METHODS: Five volunteers were each evaluated twice. On one of the randomly ordered days, epidural anesthesia (approximately T9 dermatomal level) was induced and maintained with 2-chloroprocaine. On both study days, general anesthesia was induced and maintained with isoflurane (0.7% end-tidal concentration), and core hypothermia was induced by surface cooling and continued for at least 1 h after fingertip vasoconstriction was observed. Patients undergoing colorectal surgery were randomly assigned to combined epidural/enflurane anesthesia (n = 13) or enflurane alone (n = 13). In appropriate patients, epidural anesthesia was maintained by an infusion of bupivacaine. The core temperature that triggered fingertip vasoconstriction identified the threshold. RESULTS: In the volunteers, the vasoconstriction threshold was 36.0 +/- 0.2 degrees C during isoflurane anesthesia alone, but significantly less, 35.1 +/- 0.7 degrees C, during combined epidural/isoflurane anesthesia. Cutaneous heat loss and the rates of core cooling were similar 30 min before vasoconstriction with and without epidural anesthesia. In the 30 min after vasoconstriction, heat loss decreased 33 +/- 13 W when the volunteers were given isoflurane alone, but only 8 +/- 16 W during combined epidural/isoflurane anesthesia. Similarly, the core cooling rates in the 30 min after vasoconstriction were significantly greater during combined epidural/isoflurane anesthesia (0.8 +/- 0.2 degrees C/h) than during isoflurane alone (0.2 +/- 0.1 degrees C/h). In the patients, end-tidal enflurane concentrations were slightly, but significantly, less in the patients given combined epidural/enflurane anesthesia (0.6 +/- 0.2% vs. 0.8 +/- 0.2%). Nonetheless, the vasoconstriction threshold was 34.5 +/- 0.6 degrees C in the epidural/enflurane group, which was significantly less than that in the other patients, 35.6 +/- 0.8 degrees C. When the study ended after 3 h of anesthesia, patients given combined epidural/enflurane anesthesia were 1.2 degrees C more hypothermic than those given general anesthesia alone. The rate of core cooling during the last hour of the study was 0.4 +/- 0.2 degrees C/h during combined epidural/enflurane anesthesia, but only 0.1 +/- 0.3 degrees C/h during enflurane alone. CONCLUSIONS: These data indicate that epidural anesthesia reduces the vasoconstriction threshold during general anesthesia. Furthermore, the markedly reduced rate of core cooling during general anesthesia alone illustrates the importance of leg vasoconstriction in maintaining core temperature.     

Recovery from sevoflurane anesthesia: a comparison to isoflurane and propofol anesthesia

BACKGROUND: Sevoflurane has a lower blood:gas partition coefficient than isoflurane, which may cause a more rapid recovery from anesthesia; it also might cause faster emergence times than for propofol-based anesthesia. We evaluated a database that included recovery endpoints from controlled, randomized, prospective studies sponsored by Abbott Laboratories that compared sevoflurane to isoflurane or propofol when extubation was planned immediately after completion of elective surgery in adult patients. METHODS: Sevoflurane was compared to isoflurane in eight studies (N=2,008) and to propofol in three studies (N=436). Analysis of variance was applied using least squares method mean values to calculate the pooled mean difference in recovery endpoints between primary anesthetics. The effects of patient age and case duration also were determined. RESULTS: Sevoflurane resulted in statistically significant shorter times to emergence (-3.3 min), response to command (-3.1 min), orientation (-4.0 min) and first analgesic (-8.9 min) but not time to eligibility for discharge (-1.7 min) compared to isoflurane (mean difference). Times to recovery endpoints increased with increasing case duration with isoflurane but not with sevoflurane (patients receiving isoflurane took 4-5 min more to emerge and respond to commands and 8.6 min more to achieve orientation during cases longer than 3 hr in duration than those receiving sevoflurane). Patients older than 65 yr had longer times to orientation, but within any age group, orientation was always faster after sevoflurane. There were no differences in recovery times between sevoflurane and propofol. CONCLUSIONS: Recovery from sevoflurane was 3-4 min faster than with isoflurane in all age groups, and the difference was magnified in longer-duration surgical cases (> 3 hr).     

Clinical sevoflurane metabolism and disposition. I. Sevoflurane and metabolite pharmacokinetics

BACKGROUND: Sevoflurane has low blood and tissue solubility and is metabolized to free fluoride and hexafluoroisopropanol (HFIP). Although sevoflurane uptake and distribution and fluoride formation have been described, the pharmacokinetics of HFIP formation and elimination are incompletely understood. This investigation comprehensively characterized the simultaneous disposition of sevoflurane, fluoride, and HFIP. METHODS: Ten patients within 30% of ideal body weight who provided institutional review board-approved informed consent received sevoflurane (2.7% end-tidal, 1.3 MAC) in oxygen for 3 h after propofol induction, after which anesthesia was maintained with propofol, fentanyl, and nitrous oxide. Sevoflurane and unconjugated and total HFIP concentrations in blood were determined during anesthesia and for 8 h thereafter. Plasma and urine fluoride and total HFIP concentrations were measured during and through 96 h after anesthetic administration. Fluoride and HFIP were quantitated using an ion-selective electrode and by gas chromatography, respectively. RESULTS: The total sevoflurane dose, calculated from the pulmonary uptake rate, was 88.8 +/- 9.1 mmol. Sevoflurane was rapidly metabolized to the primary metabolites fluoride and HFIP, which were eliminated in urine. HFIP circulated in blood primarily as a glucuronide conjugate, with unconjugated HFIP < or = 15% of total HFIP concentrations. In blood, peak unconjugated HFIP concentrations were less than 1% of peak sevoflurane concentrations. Apparent renal fluoride and HFIP clearances (mean +/- SE) were 51.8 +/- 4.5 and 52.6 +/- 6.1 ml/min, and apparent elimination half-lives were 21.4 +/- 2.8 and 20.1 +/- 2.6 h, respectively. Renal HFIP and net fluoride excretion were 4,300 +/- 540 and 3,300 +/- 540 mumol. Compared with the estimated sevoflurane uptake, 4.9 +/- 0.5% of the dose taken up was eliminated in the urine as HFIP. For fluoride, 3.7 +/- 0.4% of the sevoflurane dose taken up was eliminated in the urine, which, because a portion of fluoride is sequestered in bone, corresponded to approximately 5.6% of the sevoflurane dose metabolized to fluoride. CONCLUSIONS: Sevoflurane was rapidly metabolized to fluoride and HFIP, which was rapidly glucuronidated and eliminated in the urine. The overall extent of sevoflurane metabolism was approximately 5%.     

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.     

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.     

Absence of renal and hepatic toxicity after four hours of 1.25 minimum alveolar anesthetic concentration sevoflurane anesthesia in volunteers

Sevoflurane is degraded by CO2 absorbents to Compound A. The delivery of sevoflurane with a low fresh gas flow increases the generation of Compound A. The administration of Compound A to rats can produce injury to renal tubules that is dependent on both the dose and duration of exposure to Compound A. The present study evaluated renal and hepatic function in eight volunteers after a 1-L/min delivery of 3% (1.25 minimum alveolar anesthetic concentration) sevoflurane for 4 h. Volunteers gave their informed consent and provided 24-h urine collections before and for 3 days after sevoflurane anesthesia. Urine samples were analyzed for glucose, protein, albumin, and alpha- and pi-glutathione-S-transferase. Daily blood samples were analyzed for markers of renal and liver injury or dysfunction. Circuit Compound A and plasma fluoride concentrations were determined. During anesthesia, the average maximal inspired Compound A concentration was 39 +/- 6 (mean +/- SD). The median mean arterial pressure, esophageal temperature, and end-tidal CO2 were 62 +/- 6 mmHg, 36.5 +/- 0.3 degrees C, and 30.5 +/- 0.5 mm Hg, respectively. Two hours after anesthesia, the plasma fluoride concentration was 50 +/- 9 micromol/L. All markers of hepatic and renal function were unchanged after anesthesia (repeated-measures analysis of variance P > 0.05). Low-flow sevoflurane was not associated with renal or hepatic injury in humans based on unchanged biochemical markers of renal and liver function. IMPLICATIONS: Sevoflurane delivered in a 3% concentration with a fresh gas flow of 1 L/min for 4 h generated an average maximal Compound A concentration of 39 ppm but did not result in any significant increase in sensitive markers of renal function or injury, including urinary protein, albumin, glucose, and alpha- and pi-glutathione-S-transferase.     

Application of alpha-keto acid decarboxylases in biotransformations

BACKGROUND: Low-flow sevoflurane anesthesia is associated with increasing circuit concentrations of compound A, which is nephrotoxic in rats, but the effect of compound A and low-flow sevoflurane anesthesia on renal function in humans is unclear. The authors compared the effects of high- and low-flow sevoflurane and isoflurane anesthesia on renal function and on several possible markers of nephrotoxicity in humans. METHODS: Forty-two patients without preexisting renal disease underwent either low-flow isoflurane (1 l/min, n = 14), low-flow sevoflurane (1 l/min, n 14), or high-flow sevoflurane (6 l/min, n = 14) anesthesia for body-surface-area surgery scheduled to last at least 4 h. Twenty-four-hour urinary excretion of N-acetyl-beta-glucosaminidase (NAG), beta2-microglobulin, protein, glucose, blood urea nitrogen (BUN), and serum creatinine concentrations were measured before and after anesthesia. RESULTS: There were no differences in blood urea nitrogen, creatinine, and creatinine clearance among the three groups after anesthesia. Increased urinary N-acetyl-beta-glucosaminidase excretions were seen in the low-flow and high-flow sevoflurane groups, but not in the low-flow isoflurane group (P < 0.01). Ten patients in the low-flow sevoflurane group had 24-h urinary excretion of protein that exceeded the normal ranges after anesthesia, but only one patient in the isoflurane and none in the high-flow sevoflurane groups had this. CONCLUSIONS: Low-flow sevoflurane anesthesia was associated with mild and transient proteinuria. However, the observed proteinuria was not associated with any changes in blood urea nitrogen, creatinine, and creatinine clearance in these patients with no preexisting renal disease.     

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.     

Founder effect at PGL1 in hereditary head and neck paraganglioma families from the Netherlands

After repeated exposure to inhaled anesthetics, the hepatic function and metabolism of anesthetics may change. The purpose of this study was to investigate inorganic fluoride (F-) kinetics and renal and hepatic function after repeated exposure to sevoflurane. Ten patients (aged 40-70 yr) who had received sevoflurane anesthesia with a gas flow of 6 L/min for neurosurgery twice in 30-90 days were studied. Serum and urine F- concentrations were measured up to 24 h after anesthesia. Blood urea nitrogen, serum creatinine, serum and urine beta2-microglobulin, urine N-acetyl-beta-D-glucosaminidase, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin concentrations were measured up to 7 days after anesthesia. The area under the curve (AUC) of serum and urine F- concentration and half-life of serum F concentration were calculated. Urine beta2-microglobulin, AST, and ALT increased to abnormal levels after both anesthesias, with no difference between anesthesias. No measured variables, AUC of serum and urine F- concentration, or half-life of serum F- concentration showed any differences between the first and second anesthesias. In conclusion, the second exposure to sevoflurane with a high gas flow of 6 L/min in 30-90 days did not change the hepatic and renal function or affect the metabolism of sevoflurane. Implications: We studied the changes of metabolism of sevoflurane and hepatic and renal function after repeated sevoflurane anesthesia in 30-90 days. There were changes indicative of mild liver and kidney injury after sevoflurane anesthesia, but repeated exposure to sevoflurane did not enhance these changes.     

Halothane, isoflurane, and sevoflurane reduce postischemic adhesion of neutrophils in the coronary system

BACKGROUND: Polymorphonuclear neutrophils (PMNs) contribute to postischemic reperfusion damage in many organs and tissues, a prerequisite being adhesion of PMNs to vascular endothelial cells. Because adhesion processes involve orderly interactions of membrane proteins, it appeared possible that "membrane effects" of volatile anesthetics could interfere. We investigated the effects of halothane, isoflurane, and sevoflurane on postischemic adhesion of human PMNs in the intact coronary system of isolated perfused guinea pig hearts. METHODS: The hearts (n = 7-10 per group) were perfused in the "Langendorff" mode under conditions of constant flow (5 ml/min) using modified Krebs-Henseleit buffer equilibrated with 94.4% oxygen and 5.6% carbon dioxide. Global myocardial ischemia was induced by interrupting perfusion for 15 min. In the second minute of reperfusion (5 ml/min), a bolus dose of 6 x 10(5) PMNs was injected into the coronary system. The number of cells reemerging in the coronary effluent was expressed as a percentage of the total number of applied PMNs. Halothane, isoflurane, and sevoflurane, each at 1 and 2 minimal alveolar concentration (MAC), were vaporized in the gas mixture and applied from 14 min before ischemia until the end of the experiment. RESULTS: Under nonischemic conditions, 24.7 +/- 1.3% of the injected neutrophils did not reemerge from the perfused coronary system. Subjecting the hearts to global ischemia augmented retention (36.4 +/- 2.8%, P < .05). Application of halothane reduced adhesion of neutrophils to 22.6 +/- 2.1% and 24.2 +/- 1.8% at 1 and 2 MAC, respectively (P < .05). Exposure to 1 and 2 MAC isoflurane was similarly effective, whereas basal adhesion was not significantly influenced. Sevoflurane-treated hearts (1 and 2 MAC) also showed decreased adhesion of PMNs (23 +/- 2.3% and 24.8 +/- 1.8%, respectively; P < .05) and an identical reduction resulted when sevoflurane (1 MAC) was applied only with the onset of reperfusion. CONCLUSIONS: Although the mechanism of action of volatile anesthetics remains unclear in these preliminary studies, their inhibitory effect on ischemia-induced adhesion of PMNs may be beneficial for the heart during general anesthesia.     

Arterial oxygenation and shunt fraction during one-lung ventilation: a comparison of isoflurane and sevoflurane

The aim of this study was to evaluate the effect of isoflurane and sevoflurane on oxygenation and shunt fraction during one-lung ventilation (OLV). Twenty patients undergoing lobectomy for lung cancer and scheduled for long-term OLV were enrolled in this study. Patients were allocated to treatment with either isoflurane or sevoflurane. Arterial oxygenation, shunt fraction, and hemodynamics were evaluated at the end of two-lung ventilation; 20 min after the initiation of OLV; 20 min after the application of 4-cm positive end-expiratory pressure (PEEP) to the dependent lung; 20 min after 8-cm PEEP; and 20 min after the conversion from OLV to two-lung ventilation. There was no significant difference between isoflurane and sevoflurane with regard to oxygenation, shunt fraction, or hemodynamics during OLV. PaO2 values after the application of 4-cm PEEP increased from 131.1 +/- 11.8 mm Hg to 190.6 +/- 22.9 mm Hg in the isoflurane group (P < 0.05) and from 127.2 +/- 14.3 mm Hg to 192.4 +/- 26.9 mm Hg in the sevoflurane group (P < 0.05). The selection of either isoflurane or sevoflurane for OLV was made without regard to arterial oxygenation and shunt fraction. PEEP application to the dependent lung is useful for improving oxygenation during OLV, but 8-cm PEEP had no added effect compared with 4-cm PEEP. Implications: We compared the effects of isoflurane and sevoflurane on oxygenation, hemodynamics, and shunt fraction during one-lung ventilation in 20 patients undergoing scheduled lobectomy for lung cancer. There was no significant difference between isoflurane and sevoflurane with regard to oxygenation, shunt fraction, and hemodynamics during one-lung ventilation. The application of 4-cm positive end-expiratory pressure increased the partial pressure of arterial oxygen during one-lung ventilation.