Local Coupling of Cerebral Blood Flow to Cerebral Glucose Metabolism during Inhalational Anesthesia in Rats
Christian LenzThomas FrietschCarsten FüttererAnnette RebelK. van AckernWolfgang KuschinskyKlaus F. Waschke
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Background It is not known whether the effects of desflurane on local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) are different from those of other volatile anesthetics. Methods Using the autoradiographic iodoantipyrine and deoxyglucose methods, LCGU, LCBF, and their overall means were measured in 60 Sprague-Dawley rats (10 groups, n = 6 each) during desflurane and isoflurane anesthesia and in conscious controls. Results During anesthesia, mean cerebral glucose utilization was decreased compared with conscious controls: 1 minimum alveolar concentration (MAC) desflurane: -52%; 1 MAC isoflurane: -44%; 2 MAC desflurane: -62%; and 2 MAC isoflurane: -60%. Local analysis showed a reduction of LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased: 1 MAC desflurane: +40%; 1 MAC isoflurane: +43%; 2 MAC desflurane and 2 MAC isoflurane: +70%. LCBF was increased in all brain structures investigated except in the auditory cortex. No significant differences (P < 0.05) could be observed between both anesthetics for mean values of cerebral glucose use and blood flow. Correlation coefficients obtained for the relation between LCGU and LCBF were as follows: controls: 0.95; 1 MAC desflurane: 0.89; 2 MAC desflurane: 0.60; 1 MAC isoflurane: 0.87; and 2 MAC isoflurane: 0.68. Conclusion Differences in the physicochemical properties of desflurane compared with isoflurane are not associated with major differences in the effects of both volatile anesthetics on cerebral glucose utilization, blood flow, and the coupling between LCBF and LCGU.Keywords:
Desflurane
Minimum alveolar concentration
Fresh gas flow
Whether desflurane and sevoflurane have clinical advantages over isoflurane in neuroanesthesia is much debated. A porcine model was used for comparison of desflurane and sevoflurane with isoflurane with respect to their cerebrovascular effects. The minimal alveolar concentration (MAC) of each of the three agents was first determined in a standardized manner in six domestic juvenile pigs to enhance comparison reliability. Six other pigs were then anesthetized with isoflurane, desflurane, and sevoflurane, given in sequence to each pig in an even crosswise order with the first agent also used to maintain anesthesia during surgical preparation. Cerebral blood flow (CBF) was calculated from the clearance curve of intraarterially injected 133Xe. The mean arterial pressure (MAP) was invasively monitored. The estimated cerebrovascular resistance (CVRe) was calculated by dividing MAP with CBF, thereby approximating the cerebral perfusion pressure with MAP. For both MAC levels, the trend for CBF was desflurane > isoflurane > sevoflurane, and the trend for MAP and CVRe was sevoflurane > isoflurane > desflurane. Statistical comparison of desflurane and sevoflurane with isoflurane with respect to CBF and MAP revealed two statistically significant differences—namely, that CBF at 1.0 MAC desflurane was 17% higher than CBF at 1.0 MAC isoflurane (P = .0025) and that MAP at 1.0 MAC sevoflurane was 16% higher than MAP at 1.0 MAC isoflurane (P = .011). Consequently, in this study at normocapnia, these agents did not seem to differ much in their cerebral vasodilating effects at lower doses. At higher doses, however, desflurane, in contrast to sevoflurane, was found to induce more cerebral vasodilation than isoflurane.
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Minimum alveolar concentration
Normocapnia
Mean arterial pressure
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Background Volatile anesthetics facilitate surgical procedures and imaging studies in millions of children every year. Neuronal cell death after prolonged exposure to isoflurane in developing animals has raised serious concerns regarding its safe use in children. Although sevoflurane and desflurane are becoming more popular for pediatric anesthesia, their cytotoxic effects have not been compared with those of isoflurane. Accordingly, using newborn mice, the current study established the respective potencies of desflurane, isoflurane, and sevoflurane and then compared equipotent doses of these anesthetics regarding their effects on cortical neuroapoptosis. Methods Minimum alveolar concentrations were determined in littermates (aged 7-8 days, n = 42) using tail-clamp stimulation in a bracketing study design. By using equipotent doses of approximately 0.6 minimum alveolar concentration, another group of littermates was randomly assigned to receive desflurane, isoflurane, or sevoflurane or to fast in room air for 6 h. After exposure, animals (n = 47) were euthanized, neocortical apoptotic neuronal cell death was quantified, and caspase 3 activity was compared between the four groups. Results The minimum alveolar concentration was determined to be 12.2% for desflurane, 2.7% for isoflurane, and 5.4% for sevoflurane. After a 6-h exposure to approximately 0.6 minimum alveolar concentration of desflurane, isoflurane, or sevoflurane, neuronal cell death and apoptotic activity were significantly increased, irrespective of the specific anesthetic used. Conclusions In neonatal mice, equipotent doses of the three commonly used inhaled anesthetics demonstrated similar neurotoxic profiles, suggesting that developmental neurotoxicity is a common feature of all three drugs and cannot be avoided by switching to newer agents.
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Minimum alveolar concentration
Neurotoxicity
Volatile anesthetic
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Background: Traditionally, minimum alveolar concentration (MAC) has been used as the standard measure to compare the potencies of volatile anesthetics.However, it reflects the spinal mechanism of immobility rather than the subcortical mechanism of analgesia.Recently, the surgical pleth index (SPI) derived from photoplethysmographic waveform was shown to reflect the intraoperative analgesic component.This study was designed to compare the SPI values produced by equi-MAC of two commonly used volatile anesthetics, sevoflurane and desflurane.Methods: Seventy-two patients undergoing arthroscopic shoulder surgery were randomly assigned to two groups receiving either sevoflurane (n = 36) or desflurane (n = 36).General anesthesia was maintained with the respective volatile anesthetic only.A vaporizer was adjusted to maintain end-tidal anesthetic concentration at age-corrected 1.0 MAC throughout the study period.The SPI value as an analgesic estimate and the bispectral index (BIS) value as a hypnotic estimate were recorded at predefined time points during the standardized surgical procedure.Results: During the steady state of age-corrected 1.0 MAC, mean SPI values throughout the entire study period were significantly higher in the sevoflurane group than in the desflurane group (38.1 ± 12.8 vs. 30.7 ± 8.8, respectively, P = 0.005), and mean BIS values were significantly higher in the sevoflurane group than in the desflurane group (40.7 ± 5.8 vs. 36.8± 6.2, respectively, P = 0.008).Conclusions: Equi-MAC of sevoflurane and desflurane did not produce similar surgical pleth index values.Therefore, sevoflurane and desflurane may have different analgesic properties at equipotent concentrations.
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Because of its nonpungent odor and low blood-gas solubility coefficient, sevoflurane might be an ideal drug for single-breath inhaled induction of anesthesia. Fifty ASA grade I-III ambulatory surgical patients (18-76 yr old) received a single-breath induction with either 5.0% sevoflurane or 5.0% isoflurane (randomized) in a 1:1 N (2) O/O2 mixture. Anesthesia was maintained with the same anesthetic in 70% N2 O until the end of surgery, when anesthetics were abruptly discontinued. Induction times (loss of eyelash reflex) were similar for sevoflurane (75 +/- 3 s, x +/- SE) and isoflurane (67 +/- 4 s, P = not significant). Sevoflurane patients were less likely to have complications during induction (P < 0.005); coughing occurred more frequently with isoflurane (P < 0.001). During induction, heart rate increased with both sevoflurane (from 73 +/- 3 to 90 +/- 4 bpm, P < 0.05) and isoflurane (from 70 +/- 2 to 92 +/- 2 bpm, P < 0.05); the increase with isoflurane was greater than that with sevoflurane. Times to eye opening for sevoflurane (8.1 +/- 1.0 min) did not differ significantly from those for isoflurane (10.6 +/- 1.3 min). Patients opened their eyes at lower end-tidal minimum alveolar anesthetic concentration (MAC)-fractions of sevoflurane (0.12 +/- 0.01 MAC) than isoflurane (0.15 +/- 0.01 MAC, P < 0.01). During recovery, patients who received sevoflurane felt less clumsy (P < 0.001) and less confused (P < 0.005) but had higher pain scores (P < 0.005) than those who received isoflurane. Sevoflurane is more suitable than isoflurane for single-breath induction, because it produces a smoother induction with a lower incidence of complications and better patient acceptance. (Anesth Analg 1996;82:528-32)
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The effects of inhalational anaesthetic agents on survival of flaps are not well known. We investigated the effect of isoflurane and sevoflurane anaesthesia on survival of flaps using a caudally-based McFarlane skin flap in 20 male Wistar rats. Sevoflurane 1 minimum alveolar concentration (MAC) and isoflurane (1 MAC) in oxygen mixture was given to the animals. A 4×10 cm caudally-based standard McFarlane flap was raised. There were no differences in any haemodynamic values or blood gases between the sevoflurane group and the isoflurane group. Skin flaps were assessed on the seventh day. The isoflurane group had a significantly smaller area of skin flap necrosis and an increased area of flap surviving than the sevoflurane group. We conclude that survival is significantly improved when isoflurane is used as the inhalational anaesthetic rather than sevoflurane.
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Abstract Objective —To determine induction characteristics and the minimum alveolar concentration (MAC) at which consciousness returned (MAC awake ) in dogs anesthetized with isoflurane or sevoflurane. Animals —20 sexually intact male Beagles. Procedures —In experiment 1, 20 dogs were randomly assigned to have anesthesia induced and maintained with isoflurane or sevoflurane. The MAC at which each dog awoke in response to auditory stimulation (MAC awake-noise ) was determined by decreasing the end-tidal concentration by 0.1 volume (vol %) every 15 minutes and delivering a standard audible stimulus at each concentration until the dog awoke. In experiment 2, 12 dogs received the same anesthetic agent they were administered in experiment 1. After duplicate MAC determination, the end-tidal concentration was continually decreased by 10% every 15 minutes until the dog awoke from anesthesia (MAC awake ). Results —Mean induction time was significantly greater for isoflurane-anesthetized dogs (212 seconds), compared with the sevoflurane-anesthetized dogs (154 seconds). Mean ± SD MAC awake-noise was 1.1 ± 0.1 vol % for isoflurane and 2.0 ± 0.2 vol % for sevoflurane. Mean MAC was 1.3 ± 0.2 vol % for isoflurane and 2.1 ± 0.6 vol % for sevoflurane, and mean MAC awake was 1.0 ± 0.1 vol % for isoflurane and 1.3 ± 0.3 vol % for sevoflurane. Conclusions and Clinical Relevance —Sevoflurane resulted in a more rapid induction than did isoflurane. The MAC awake for dogs was higher than values reported for both agents in humans. Care should be taken to ensure that dogs are at an appropriate anesthetic depth to prevent consciousness, particularly when single-agent inhalant anesthesia is used.
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The anesthetic requirements for sevoflurane, isoflurane, and halothane were determined in mongrel dogs. The MACs (minimum alveolar concentration) of sevoflurane, isoflurane, and halothane were 2.36 +/- 0.46% (n = 18), 1.39 +/- 0.25% (n = 10), and 0.89 +/- 0.20% (n = 12), respectively (mean +/- SD). In agreement with sevoflurane's low blood/gas partition coefficient (0.6), the rate of rise of alveolar concentration toward that inspired (FA/FI) for sevoflurane was significantly faster than that for either halothane or isoflurane. Thirty seconds after breathing a constant inspired concentration FA/FI was 0.75 for sevoflurane, which was 2.96 times higher than that with halothane (0.25 +/- 0.02) and 1.29 times higher than that with isoflurane (0.6 +/- 0.05). Induction with sevoflurane was smooth, with no struggling nor excessive salivation.
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Background: In this study we aimed to compare haemodynamics, body temperature, inspired and expired oxygen and anaesthetic gas concentrations in minimal and medium flow anaesthesia with isoflurane and desflurane. Methods: We studied 60 ASA 1-2 patients undergoing elective surgical procedures Patients were randomly divided to two equal main groups to receive isoflurane and desflurane. Then these main groups were randomly divided to 3 equal sub-groups such as to receive isoflurane or desflurane in 500, 1000 and 2000 ml.min fresh gas flow (FGF) respectively. FGF was applied 4 L min in initial phase (10 min) after standard anaesthetic induction, then isoflurane and desflurane concentrations were adjusted as 1.5 % and 6 % respectively and FGF was adjusted according to groups. HR, MAP, SpO oesophageal temperature, vaporizer settings, inspired and expired anaesthetic gas concentrations were recorded at regular intervals throughout the study. Results: Inspired and expired anaesthetic concentrations were decreased significantly in minimal flow groups compared to medium and high flow groups. FiO2 values were decreased parallel to duration of anaesthesia. Low FiO occurred in 2 cases in minimal flow isoflurane group and 8 cases in minimal flow desflurane group. Conclusion: Isoflurane and desflurane could be used safely with minimal and medium FGF, but we decided that isoflurane was superior to desflurane regarding oxygenation. We thought that there was hypoxia risk in cases which desflurane was used as inhalant agent in minimal flow with 50 % NO in O. However, we concluded that the increasing FiO % ratio can prevent hypoxia.
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Objective To compare the effects of sevoflurane,isoflurane and desflurane on transcranial electrical motor evoked potentials(MEPs)in patients undergoing neurosurgery.Methods Sixty ASA Ⅰ or Ⅱ patients aged 18-64 yr undergoing neurosurgery were randomly divided into 3 groups(n = 20 each): sevoflurane group,isoflurane group and desflurane group.BIS value and MEPs were monitored.The end-tidal concentrations of sevoflurane,isoflurane and desflurane were adjusted and maintained at 0.50,0.75,1.00 and 1.30 MAC respectively for at least 15 min during 6 stimuli delivered at 1000 Hz and 300 V lasting for 75 μs.The amplitudes and latency of MEPs and BIS value were recorded before administration(baseline)and the each stable state (T1-4).The failure rate of MEPs was also recorded.Results The amplitude of MEPs and BIS value were significantly decreased at T1.2 and the latency of MEPs was prolonged at T1-4 in desflurane group compared with sevoflurane and isoflurane groups(P＜0.05).There was no significant difference in the amplitudes and latency of MEPs and BIS value between group sevoflurane and isoflurane(P＞0.05).The failure rates of MEPs were 0 at baseline,T1 and T2,0,5% and 20% at T3 ,and 5%,20% and 45% at T4 in sevoflurane,isoflurane and desflurane groups respectively.The failure rate of MEPs was significantly higher in desflurane group than in sevoflurane and isoflurane groups(P＜0.05).Conclusion Desflurane has greater suppressive effect on MEPs than sevoflurane and isoflurane.1.00 MAC of sevoflurane and isoflurane,while 0.75-1.00 MAC of desflurane may be the suitable end-tidal concentration for MEP monitoring.
Key words:
Anesthetics,inhalation; Isoflurane; Evoked potentials,motor; Electric stimulation
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We tested the prediction that the alveolar washin and washout, tissue time constants, and pulmonary recovery (volume of agent recovered during washout relative to the volume taken up during washin) of desflurane, sevoflurane, isoflurane, and halothane would be defined primarily by their respective solubilities in blood, by their solubilities in tissues, and by their metabolism. We concurrently administered approximately one-third the MAC of each of these anesthetics to five young female swine and determined (separately) their solubilities in pig blood and tissues. The bloodigas partition coefficient of desflurane (0.35 ± 0.02) was significantly smaller (P < 0.01) than that of sevoflurane (0.45 ± 0.02), isoflurane (0.94 ± 0.05), and halothane (2.54 ± 0.21). Tissueiblood partition coefficients of desflurane and halothane were smaller than those for the other two anesthetics (P < 0.05) for all tissue groups. As predicted from their blood solubilities, the order of washin and washout was desflurane, sevoflurane, isoflurune, and halothane (most to least rapid). As predicted from tissue solubilities, the tissue time constants for desflurane were smaller than those for sevoflurane, isoflurane, and halothane. Recovery (normalized to that of isoflurane) of the volume of anesthetic taken up was significantly greater (P < 0.05) for desflurane (93% ± 7% [mean ± SD]) than for halothane (77% ± 6%), was not different from that of isoflurane (100%), but was less than that for sevoflurane (111% ± 17%). The lower value for halothane is consistent with its known metabolism, but the lower (than sevoflurane) value for desflurane is at variance with other presently available data for their respective biodegradations.
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Washout
Enflurane
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