Comparison of volatile anesthetic actions on intracellular calcium stores of vascular smooth muscle: investigation in isolated systemic resistance arteries

BACKGROUND: Volatile anesthetic actions on intracellular Ca2+ stores (ie., sarcoplasmic reticulum [SR]) of vascular smooth muscle have not been fully elucidated. METHODS: Using isometric force recording method and fura-2 fluorometry, the actions of four volatile anesthetics on SR were studied in isolated endothellum-denuded rat mesenteric arteries. RESULTS: Halothane (> or = 3%) and enflurane (> or = 3%), but not isoflurane and sevoflurane, increased the intracellular Ca2+ concentration ([Ca2+]i) in Ca2+-free solution. These Ca2+-releasing actions were eliminated by procaine. When each anesthetic was applied during Ca2+ loading, halothane (> or = 3%) and enflurane (5%), but not isoflurane and sevoflurane, decreased the amount of Ca2+ in the SR. However, if halothane or enflurane was applied with procaine during Ca2+ loading, both anesthetics increased the amount of Ca2+ in the SR. The caffeine-induced increase in [Ca2+], was enhanced in the presence of halothane (> or = 1%), enflurane (> or = 1%), and isoflurane (> or = 3%) but was attenuated in the presence of sevoflurane (> or = 3%). The norepinephrine-induced increase in [Ca2+], was enhanced only in the presence of sevoflurane (> or = 3%). Not all of these anesthetic effects on the [Ca2+]i were parallel with the simultaneously observed anesthetic effects on the force. CONCLUSIONS: In systemic resistance arteries, the halothane, enflurane, isoflurane, and sevoflurane differentially influence the SR functions. Both halothane and enflurane cause Ca2+ release from the caffeine-sensitive SR. In addition, both anesthetics appear to have a stimulating action on Ca2+ uptake in addition to the Ca2+-releasing action. Halothane, enflurane, and isoflurane all enhance, while sevoflurane attenuates, the Ca2+-induced Ca2+-release mechanism. However, only sevoflurane stimulates the inositol 1,4,5-triphosphate-induced Ca2+ release mechanism. Isoflurane and sevoflurane do not stimulate Ca2+ release or influence Ca2+ uptake.     

Preservation of the Ratio 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 4 h 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.     

The anticonvulsant effects of volatile anesthetics on penicillin-induced status epilepticus in cats

Volatile anesthetics may be used to treat status epilepticus when conventional drugs are ineffective. We studied 30 cats to compare the inhibitory effects of sevoflurane, isoflurane, and halothane on penicillin-induced status epilepticus. Anesthesia was induced and maintained with one of the three volatile anesthetics in oxygen. Penicillin G was injected into the cisterna magna, and the volatile anesthetic discontinued. Once status epilepticus was induced (convulsive period), the animal was reanesthetized with 0.6 minimum alveolar anesthetic concentration (MAC) of the volatile anesthetic for 30 min, then with 1.5 MAC for the next 30 min. Electroencephalogram and multiunit activity in the midbrain reticular formation were recorded. At 0.6 MAC, all anesthetics showed anticonvulsant effects. Isoflurane and halothane each abolished the repetitive spike phase in one cat; isoflurane reduced the occupancy of the repetitive spike phase (to 27%+/-22% of the convulsive period (mean +/- SD) significantly more than sevoflurane (60%+/-29%; P < 0.05) and halothane (61%+/-24%; P < 0.05), and the increase of midbrain reticular formation with repetitive spikes was reduced by all volatile anesthetics. The repetitive spikes were abolished by 1.5 MAC of the anesthetics: in 9 of 10 cats by sevoflurane, in 9 of 9 cats by isoflurane, and in 9 of 11 cats by halothane. In conclusion, isoflurane, sevoflurane, and halothane inhibited penicillin-induced status epilepticus, but isoflurane was the most potent. IMPLICATIONS: Convulsive status epilepticus is an emergency state and requires immediate suppression of clinical and electrical seizures, but conventional drugs may be ineffective. In such cases, general anesthesia may be effective. In the present study, we suggest that isoflurane is preferable to halothane and sevoflurane to suppress sustained seizure.     

The effects of sevoflurane, halothane, enflurane, and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs.

Inhalational anesthetics produce differential effects on hepatic blood flow and oxygenation that may impact hepatocellular function and drug clearance. In this investigation, the effects of sevoflurane on hepatic blood flow and oxygenation were compared with those of enflurane, halothane, and isoflurane in ten chronically instrumented greyhound dogs. Each dog randomly received enflurane, halothane, isoflurane, and sevoflurane, each at 1.0, 1.5, and 2.0 MAC concentrations. Mean arterial blood pressure and cardiac output decreased in a dose-dependent fashion during all four anesthetics studied. Heart rate increased compared to control during enflurane, isoflurane, and sevoflurane anesthesia and did not change during halothane anesthesia. Hepatic arterial blood flow and portal venous blood flow were measured by chronically implanted electromagnetic flow probes. Hepatic O2 delivery and consumption were calculated after hepatic arterial, portal venous, and hepatic venous blood gas analysis. Hepatic arterial blood flow was maintained with sevoflurane and isoflurane. Halothane and enflurane reduced hepatic arterial blood flow during all anesthetic levels compared to control (P less than 0.05), with marked reductions occurring with 1.5 and 2.0 MAC halothane concomitant with an increase in hepatic arterial vascular resistance. Portal venous blood flow was reduced with isoflurane and sevoflurane at 1.5 and 2.0 MAC. A somewhat greater reduction in portal venous blood flow occurred during 2.0 MAC sevoflurane (P less than 0.05 compared to control and 1.0 MAC values for sevoflurane). Enflurane reduced portal venous blood flow at 1.0, 1.5, and 2.0 MAC compared to control. Halothane produced the greatest reduction in portal venous blood flow (P less than 0.05 compared to sevoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)     

The theoretical ideal fresh-gas flow sequence at the start of low-flow anaesthesia

A spreadsheet model of a circle breathing system and a 70-kg anaesthetised 'standard man' has been used to simulate the first 20 min of low-flow anaesthesia with halothane, enflurane, isoflurane, sevoflurane and desflurane in oxygen. It is shown that, with the fresh-gas flow set initially equal to the total ventilation and the fresh-gas partial pressure to 3 MAC, the end-expired partial pressure can be raised to 1 MAC in 1 min with desflurane and sevoflurane, 1.5 min with isoflurane, 2.5 min with enflurane and 4 min with halothane. Sequences of lower fresh-gas flow and partial pressure settings are given for then maintaining 1 MAC end-expired partial pressure, with a minimum usage of anaesthetic, e.g. 13 ml of liquid desflurane in 20 min (of which only 33% is taken up by the patient) if the minimum acceptable flow is 1 lmin⁻¹, or 8 ml (with 57% in the patient) if the minimum is 250 mlmin⁻¹.     

Volatile anesthetics regulate pulmonary vascular tension through different potassium channel subtypes in isolated rabbit lungs

BACKGROUND: The effects of volatile anesthetics on subtypes of K(+) channels located on pulmonary vessels remain largely unexplored. METHODS: To investigate whether or not potassium channels play a role in the effect of volatile anesthetic on pulmonary vessels, isolated and perfused rabbit lungs were divided into four groups (n = 7 each): a control group without treatment, a glibenclamide (Glib) group treated with adenosine triphosphate-sensitive K(+) (K(ATP)) channel inhibitor, a 4-aminopyridine (4-AP) group treated with voltage-sensitive K(+) (K(V)) channel inhibitor, and an iberiotoxin (IbTX) group treated with high conductance calcium-activated K(+) (K(Ca)) channel inhibitor. After inhibitor administration and stabilization, two minimum alveolar concentration (MAC) of halothane, enflurane, isoflurane, or 1.8 MAC of sevoflurane were randomly administered for 15 min followed by eight minutes of fresh gas mixture after each agent inhalation. RESULTS: Isoflurane did not change pulmonary vascular tension in the control group but instead constricted the pulmonary vessels when K(V) channels were inhibited with 4-AP; constrictive effects of enflurane and halothane were observed on pulmonary vessels, and were enhanced by K(V) channel inhibition with 4-AP, but they were inhibited by K(Ca) channel inhibition with IbTX; the dilation effect of sevoflurane was observed on pulmonary vessels but was not significantly affected by any of the K(+) channel inhibitors. CONCLUSION: Halothane, enflurane and isoflurane, but not sevoflurane, regulate pulmonary vascular tension through K(V) and/or K(Ca) channels in isolated rabbit lungs.     

Carbon monoxide production from desflurane, enflurane, halothane, isoflurane, and sevoflurane with dry soda lime.

BACKGROUND: Previous studies in which volatile anesthetics were exposed to small amounts of dry soda lime, generally controlled at or close to ambient temperatures, have demonstrated a large carbon monoxide (CO) production from desflurane and enflurane, less from isoflurane, and none from halothane and sevoflurane. However, there is a report of increased CO hemoglobin in children who had been induced with sevoflurane that had passed through dry soda lime. Because this clinical report appears to be inconsistent with existing laboratory work, the authors investigated CO production from volatile anesthetics more realistically simulating conditions in clinical absorbers. METHODS: Each agent, 2.5 or 5% in 2 l/min oxygen, were passed for 2 h through a Dr?ger absorber canister (bottom to top) filled with dried soda lime (Dr?gersorb 800). CO concentrations were continuously measured at the absorber outlet. CO production was calculated. Experiments were performed in ambient air (19-20 degrees C). The absorbent temperature was not controlled. RESULTS: Carbon monoxide production peaked initially and was highest with desflurane (507 +/- 70, 656 +/- 59 ml CO), followed by enflurane (460 +/- 41, 475 +/- 99 ml CO), isoflurane (176 +/- 2.8, 227 +/- 21 ml CO), sevoflurane (34 +/- 1, 104 +/- 4 ml CO), and halothane (22 +/- 3, 20 +/- 1 ml CO) (mean +/- SD at 2.5 and 5%, respectively). CONCLUSIONS: The absorbent temperature increased with all anesthetics but was highest for sevoflurane. The reported magnitude of CO formation from desflurane, enflurane, and isoflurane was confirmed. In contrast, a smaller but significant CO formation from sevoflurane was found, which may account for the CO hemoglobin concentrations reported in infants. With all agents, CO formation appears to be self-limited.     

Minimum alveolar anesthetic concentration of volatile anesthetics in normal and cardiomyopathic hamsters

Minimum alveolar anesthetic concentrations (MAC) values of volatile anesthetics in cardiovascular diseases remain unknown. We determined MAC values of volatile anesthetics in spontaneously breathing normal and cardiomyopathic hamsters exposed to increasing (0.1%-0.3% steps) concentrations of halothane, isoflurane, sevoflurane, or desflurane (n = 30 in each group) using the tail-clamp technique. MAC values and their 95% confidence interval were calculated using logistic regression. In normal hamsters, inspired MAC values were: halothane 1.15% (1.10%-1.20%), isoflurane 1.62% (1.54%-1.69%), sevoflurane 2.31% (2.22%-2.40%), and desflurane 7.48% (7.30%-7.67%). In cardiomyopathic hamsters, they were: halothane 0.89% (0.83%-0.95%), isoflurane 1.39% (1.30%-1.47%), sevoflurane 2.00% (1.85%-2.15%), and desflurane 6.97% (6.77%-7.17%). Thus, MAC values of halothane, isoflurane, sevoflurane, and desflurane were reduced by 23% (P < 0.05), 14% (P < 0.05), 13% (P < 0.05), and 7% (P < 0.05), respectively in cardiomyopathic hamsters. IMPLICATIONS: Minimum alveolar anesthetic concentrations of volatile anesthetics were significantly lower in cardiomyopathic hamsters than in normal hamsters.     

Carbon Monoxide Production from Desflurane, Enflurane, Halothane, Isoflurane, and Sevoflurane with Dry Soda Lime

Background : Previous studies in which volatile anesthetics were exposed to small amounts of dry soda lime, generally controlled at or close to ambient temperatures, have demonstrated a large carbon monoxide (CO) production from desflurane and enflurane, less from isoflurane, and none from halothane and sevoflurane. However, there is a report of increased CO hemoglobin in children who had been induced with sevoflurane that had passed through dry soda lime. Because this clinical report appears to be inconsistent with existing laboratory work, the authors investigated CO production from volatile anesthetics more realistically simulating conditions in clinical absorbers.

Methods : Each agent, 2.5 or 5% in 2 l/min oxygen, were passed for 2 h through a Drager absorber canister (bottom to top) filled with dried soda lime (Dragersorb 800). CO concentrations were continuously measured at the absorber outlet. CO production was calculated. Experiments were performed in ambient air (19-20[degrees]C). The absorbent temperature was not controlled.

Results : Carbon monoxide production peaked initially and was highest with desflurane (507 +/- 70, 656 +/- 59 ml CO), followed by enflurane (460 +/- 41, 475 +/- 99 ml CO), isoflurane (176 +/- 2.8, 227 +/- 21 ml CO), sevoflurane (34 +/- 1, 104 +/- 4 ml CO), and halothane (22 +/- 3, 20 +/- 1 ml CO) (mean +/- SD at 2.5 and 5%, respectively).     

Comparative effects of halothane, isoflurane, and sevoflurane on the liver with hepatic artery ligation in the beagle.

Recently, there has been increasing interest in the alterations in splanchnic and hepatic circulation and preservation of hepatic oxygenation and function during anesthesia and surgery. However, the effects of volatile anesthetics under a condition of marginal hepatic oxygen supply are not well understood. Using a crossover design, we therefore studied the effects of equianesthetic concentrations (1.5 MAC) of halothane, isoflurane, and sevoflurane on hepatic oxygenation and function in nine beagles in which the hepatic artery had been ligated. Portal blood flow was measured by an electro-magnetic flow meter. Hepatic function was assessed by indocyanine green elimination kinetics. While cardiac output and mean arterial pressure were greater during halothane anesthesia than during isoflurane and sevoflurane anesthesia, portal blood flow and hepatic oxygen supply were significantly less during halothane and sevoflurane anesthesia than during isoflurane anesthesia. With regard to hepatic oxygen uptake, there was a significant difference between halothane (2.7 +/- 1.2 ml.min-1 x 100 g-1) and sevoflurane (3.7 +/- 2.0 ml.min-1 x 100 g-1; P less than 0.05). Consequently, the hepatic oxygen supply/uptake ratio and the hemoglobin oxygen saturation and oxygen partial pressure in hepatic venous blood during sevoflurane anesthesia were significantly less than they were with the other anesthetics. Indocyanine green clearance was better preserved during sevoflurane anesthesia (39.7 +/- 12.0 ml.min-1) than during halothane anesthesia (30.9 +/- 8.4 ml.min-1; P less than 0.05). We conclude that sevoflurane is accompanied by a smaller oxygen supply/uptake ratio than is halothane and isoflurane, while it preserves hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential effects of halothane,enflurane, isoflurane,and sevoflurane on the hemodynamics and metabolism in the perfused rat liver in fasted rats

The effects of volatile anesthetics on hepatic hemodynamics and metabolism were studied using isolated liver perfusion. The liver was isolated from overnight-fasted male Sprague-Dawley rats and placed in a recirculating perfusion-aeration system. The liver was perfused through the portal vein at a constant pressure of 12 cmH₂O. Four volatile anesthetics, halothane, enflurane, isoflurane, and sevoflurane, were administered at concentrations identical to 1 and 2 times the minimal alveolar concentration (MAC). All the anesthetics maintained hepatic flow and decreased hepatic oxygen consumption. Among the anesthetics tested, isoflurane produced the largest decrease in hepatic oxygen consumption. At 2 MAC, the percent decrease in oxygen consumption by isoflurane was significantly greater than that by halothane. The increase in lactate concentration in the recirculating perfusate was significantly enhanced by the volatile anesthetics, and the enhancement was less remarkable in the isofluranetreated group than in the enflurane-or sevoflurane-treated groups. These results indicate that volatile anesthetics alter hepatic carbohydrate metabolism but maintain hepatic blood flow when the perfusion pressure is kept constant. Isoflurane exerts exceptional influence on hepatic oxygen consumption and lactate production, and may be preferable for operations that limit the oxygen supply to the liver.     

Vecuronium-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans

To determine the effect of the commonly used volatile anesthetics on a vecuronium-induced neuromuscular blockade, the authors studied 54 patients anesthetized with 1.2 MAC or 2.2 MAC enflurane, isoflurane, or halothane (MAC value includes contribution from 60% nitrous oxide). During 1.2 MAC enflurane, isoflurane, and halothane, the ED50S (the doses depressing twitch tension 50%) for vecuronium were 12.8, 14.7, and 16.9 micrograms/kg, respectively. During 2.2 MAC enflurane, isoflurane, and halothane, the ED50S for vecuronium were 6.3, 9.8, and 13.8 micrograms/kg, respectively (P less than 0.05). Time from injection to peak effect was the same for each anesthetic group (6.5 +/- 0.5 min, mean +/- SD), except for the group given 2.2 MAC enflurane (9.7 +/- 0.6 min) (P less than 0.05). The duration of a 50% block from injection to 90% recovery was the same for each group (mean 20 +/- 4 min), except for the group given 2.2 MAC enflurane (46.5 min) (P less than 0.05). The authors conclude that enflurane is the most potent volatile anesthetic, followed by isoflurane and then halothane, in augmenting a vecuronium-induced neuromuscular blockade. Increasing the concentration of volatile anesthetic has less effect on a neuromuscular blockade produced by vecuronium than on one produced by other nondepolarizing relaxants (e.g., pancuronium and d-tubucurarine).     

麻醉药在低流量紧闭麻醉环路内分布的实验研究

对低流量紧闭麻醉环路内注药的分布，以及环路外挥发器释出药物及其环路内稀释进行实验研究。结果显示，吸入段注入 １ｍｌ三种含氟麻醉药液体产生较高的吸入浓度峰值，均在 １％或更多，呼出段注药２ｍｌ则不然，最高不过１．７％，但可控性差。注药１ｍｌ后３０分，环路内橡皮和塑料对麻醉药的吸收以安氟醚最大（３０％），而新鲜钠石灰对麻醉药的摄取则是七氟醚最多（６２％）。环路外挥发器在５００ｍｌ／ｍｉｎ的低流量下，开至刻度“５”，经稀释后的吸入浓度上升缓慢，５分时安氟醚的吸入浓度仍不足１％，难以适应麻醉诱导的需要。     

Comparison of halothane, enflurane, and isoflurane with nitrous oxide on contractility and oxygen supply and demand in isolated hearts.

The authors' aim was to examine direct cardiac responses to isoflurane, enflurane and halothane, as altered during mild hypoxia by the substitution of nitrogen (N2) for oxygen (O2), and additionally by the substitution of nitrous oxide (N2O) for N2. Heart rate, atrioventricular conduction time, left ventricular pressure (LVP), peak positive and negative derivatives of LVP (dLVP/dtmax), coronary flow, O2 delivery (DO2), percent O2 extraction, and myocardial O2 consumption (MVo2) were examined in 47 isolated guinea pig hearts. Changes in the ratio of DO2 to MVO2 indicated the relationship of autoregulation of coronary flow to myocardial O2 utilization. Each heart was first exposed to 96% O2 and then randomly exposed to 48% N2 and 48% N2O alone and with three equivalent concentrations of one of three volatile anesthetics: isoflurane (n = 15), halothane (n = 16), or enflurane (n = 16). Results were as follows: 1) N2 alone significantly decreased LVP, +dLVP/dtmax and -dLVP/dtmax, DO2 and MVO2; increased coronary flow; and produced no change in heart rate, atrioventricular conduction time, percent O2 extraction, or the DO2/MVO2 ratio. 2) Compared to N2, N2O alone only produced additional significant decreases in LVP and +dLVP/dtmax. 3) In the presence of N2 or N2O, each volatile anesthetic caused significant stepwise decreases in heart rate, LVP, +dLVP/dtmax and -dLVP/dtmax, MVO2, and percent O2 extraction; no additional change in coronary flow or DO2; and a stepwise increase in the DO2/MVO2 ratio. The effects of halothane and enflurane were generally greater than those of isoflurane. 4) Each volatile anesthetic caused an additive, parallel depression of LVP and percent O2 extraction as a function of MAC with N2O compared to N2. This study demonstrates that the direct negative inotropic effects of halothane and enflurane are more pronounced than those of isoflurane and are accompanied by a greater reduction in O2 utilization by halothane and enflurane than by isoflurane in the presence of mild hypoxia alone or with the addition of N2O. The study also demonstrates that N2O accentuates the negative inotropic effects of volatile anesthetics during reduced O2.     

The nonlinear potency of sub-MAC concentrations of nitrous oxide in decreasing the anesthetic requirement of enflurane, halothane, and isoflurane in rats

The effect of nitrous oxide (N2O) on the MAC of enflurane, halothane, and isoflurane was determined in male rats. Each rat received either enflurane, halothane, or isoflurane, along with 0%, 15%, or 75% N2O. Anesthetic equilibration was verified by mass spectrometry sampling of end-tidal gases. MAC was determined at each N2O concentration by the standard tail clamp method. The N2O dose-response data for each animal were fit by a second-order polynomial equation to estimate the value of a second-order coefficient. A linear dose-response would result in a value of zero, whereas the extent to which the data deviate from nonlinearity would be reflected by an increase in the value of this coefficient. The null hypothesis, that the second-order coefficient should be zero, was tested by a one-sample two-tailed t test. The volatile anesthetic requirement decreased as the N2O concentration increased; however, it did not do so linearly. For each of the three volatile anesthetic groups, the second-order coefficients were consistently greater than zero (P less than 0.05). These data are not consistent with the accepted presumption that the summation of N2O with volatile anesthetics is linear.     

Comparison of the effects of volatile anesthetics on brain glucose metabolism in rats

The objective of this investigation was to compare the effects of the commonly used volatile anesthetics on concentrations of plasma and cerebral glucose and cerebral intermediary metabolites. Fasted male Long-Evans rats were anesthetized with a volatile anesthetic and, after tracheostomy and paralysis, were mechanically ventilated. Each of three groups received one MAC concentration of anesthesia with halothane, enflurane, or isoflurane. At the end of 60-75 min of anesthesia, blood was sampled for arterial blood gas and plasma glucose analysis, and the brain was rapidly sampled and frozen for analysis of energy metabolites. Physiologic variables were maintained as follows: PaCO2 30-40 mmHg, pHa 7.20-7.40, PaO2 greater than 60 mmHg, MAP greater than 60 mmHg, and rectal temperature 37.5-38.5 degrees C. Mean plasma glucose concentrations in the three groups were as follows (muMol/ml +/- SEM): halothane, 7.45 /- .62; enflurane, 6.95 +/- .22; isoflurane, 10.11 +/- 1.00. Mean brain glucose concentrations in the three groups were (muMol/gm wet weight): halothane, 2.04 +/- .20; enflurane, 2.07 +/- .26; isoflurane, 3.04 +/- .31. Plasma and brain glucose levels were significantly increased in the isoflurane group compared to the other two groups (P less than .05) with no differences occurring in the brain/plasma glucose ratio among the three groups. No differences were present between groups in brain lactate, pyruvate, fructose diphosphate, malate, alpha-ketoglutarate, phosphocreatine, or adenine nucleotides. Thus, at one MAC concentration, major differences between volatile anesthetics on brain energy availability are not present, although isoflurane raised cerebral glucose levels.     

Blood Flow Velocity of Middle Cerebral Artery during Prolonged Anesthesia with Halothane, Isoflurane, and Sevoflurane in Humans

Background: It is not clear whether the increase of cerebral blood flow (CBF) produced by volatile anesthetics is maintained during prolonged anesthesia. In a previous study, the authors found that CBF equivalent, an index of flow-metabolism relationship, was stable over 3 h, suggesting no decay over time in CBF for 3 h during volatile anesthesia in humans. However, it may be possible that CBF changes in a parallel fashion to functional metabolic changes. In this study, to estimate the response of CBF to three volatile anesthetics, the authors used transcranial Doppler (TCD) ultrasonography to measure time-averaged mean velocity in the middle cerebral artery (Vmca).

Methods: Twenty-four surgical patients were randomly assigned to three groups to receive halothane, isoflurane, or sevoflurane (eight patients, each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5, 1.0, and 1.5 MAC before surgery and then at 1.5 MAC during surgery, which lasted more than 3 h. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 70 mmHg, using phenylephrine infusion, if necessary. TCD recordings of the Vmca were performed continuously.

Results: Vmca at 0.5 MAC of halothane, isoflurane, and sevoflurane was 49 +/- 19, 57 +/- 8, and 48 +/- 13 cm/s, respectively. Halothane significantly (P < 0.01) increased Vmca in a dose-dependent manner (0.5, 1.0, 1.5 MAC), whereas isoflurane and sevoflurane produced no significant dose-related changes. At 1.5 MAC for 3 h, Vmca changed significantly (P < 0.05) for the time trends, but it did not exhibit decay over time with all drugs. During burst suppression, observed electroencephalographically (EEG) on patients during isoflurane and sevoflurane anesthesia, the onset of a burst increased Vmca (approximately 5-30 cm/s), which was maintained for the duration of the burst.     

Effects of sevoflurane, isoflurane, enflurane, and halothane on left ventricular diastolic performance in dogs

The effects of volatile anesthetics on active (ventricular relaxation) and passive (chamber stiffness) indices of diastolic function and on left ventricular filling rates in dogs were studied to determine how these agents affect left ventricular diastolic performance. Thirty-five mongrel dogs were randomly assigned to receive sevoflurane, isoflurane, enflurane, or halothane. Left ventricular pressure waveforms, phonocardiograms, and echocardiograms were recorded after administering the anesthetics at concentrations of 0% (control), 1%, 2%, and 3%. Ventricular relaxation was defined as the time constant of the decline in left ventricular pressure. Chamber stiffness was derived from the ventricular pressure-volume relationship during passive filling. Rapid filling rate, slow filling rate, and atrial filling rate were obtained from echocardiograms and phonocardiograms. No change in the time constant or in chamber stiffness was observed at any concentration of sevoflurane or isoflurane. However, the highest studied concentration of enflurane and halothane produced a significant increase in the time constant and in chamber stiffness. Rapid filling rate as well as atrial filling rate decreased significantly with the volatile anesthetics, especially with enflurane and halothane. Sevoflurane and isoflurane did not alter ventricular relaxation or chamber stiffness, but did affect diastolic function as manifested by their alteration of filling rates. In contrast, enflurane and halothane each prolonged ventricular relaxation and increased chamber stiffness. With the administration of the volatile anesthetics, the rapid filling rate decreased with the deterioration of diastolic function; in addition, atrial filling rates decreased and did not compensate for the reduction in early ventricular filling.     

Volatile Anesthetics Depress Spinal Motor Neurons

Background: Depression of spinal alpha-motor neurons apparently plays a role in the surgical immobility induced by isoflurane. Using the noninvasive technique of F-wave analysis, the authors tested the hypothesis that depressed motor neuron excitability is an effect common to other clinically relevant inhaled anesthetics.

Methods: The authors measured F-wave amplitude in rats anesthetized with desflurane, enflurane, halothane, or sevoflurane. Each animal received one anesthetic at five equipotent anesthetic concentrations (0.6, 0.8, 1.2, and 1.6 minimum alveolar concentration [MAC] and 0.8 MAC with 65% N2 O). F waves were detected as late potentials in electromyographic responses evoked in the intrinsic muscles of the hind paw after monopolar stimulation of the ipsilateral posterior tibial nerve.

Results: All tested inhaled anesthetics depressed F-wave amplitude but not M-wave (orthodromic, early muscle activation) amplitude, and increased M-F latency in a dose-dependent manner. At 1.0 MAC, the estimated F/M ratio was 70+/-13% SD of that at baseline (0.6 MAC). Nitrous oxide added to 0.8 MAC of the potent vapors depressed F/M ratio by 63+/-17%.     

Effects of halothane, enflurane, isoflurane, and nitrous oxide on somatosensory evoked potentials in humans

Median nerve somatosensory evoked potentials (SSEPs) were recorded in 21 healthy subjects anesthetized with halothane, isoflurane, or enflurane (with and without nitrous oxide) for abdominal or pelvic surgery. Recordings were made prior to induction, then at 0.5 MAC increments of each volatile agent with 60% N2O up to 1.5 MAC, and, finally, at 1.5 MAC without N2O. All three volatile anesthetics produced dose-related reductions in the amplitude and increases in the latency of the cortical component of the SSEP. These changes were most pronounced with enflurane and least with halothane. At 1.5 MAC of each volatile agent, cortical latency decreased and amplitude increased when nitrous oxide was discontinued. The results suggest that in neurologically intact patients, end-tidal concentrations of 1.0 MAC halothane and 0.5 MAC enflurane or isoflurane (each in 60% N2O) can be compatible with effective SSEP monitoring. Volatile anesthetic concentrations consistent with satisfactory somatosensory-evoked potential recording may be greater if N2O is not employed.