Pharmacokinetics of desflurane, sevoflurane, isoflurane, and halothane in pigs

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 blood/gas partition coefficient of desflurane (0.35 +/- 0.02) was significantly smaller (P less than 0.01) than that of sevoflurane (0.45 +/- 0.02), isoflurane (0.94 +/- 0.05), and halothane (2.54 +/- 0.21). Tissue/blood partition coefficients of desflurane and halothane were smaller than those for the other two anesthetics (P less than 0.05) for all tissue groups. As predicted from their blood solubilities, the order of washin and washout was desflurane, sevoflurane, isoflurane, 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 less than 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.     

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.     

Comparative hemodynamic depression of halothane versus isoflurane in neonates and infants: an echocardiographic study.

The purpose of this study was to measure and compare the relationship of cardiovascular depression and dose during equal potent levels of halothane and isoflurane anesthesia in neonates (n = 19) (16.7 +/- 6.9 days) and infants (n = 54) (6.1 +/- 3.1 mo). Seventy-three children had heart rate, arterial blood pressure, and pulsed Doppler pulmonary blood flow velocity as well as two-dimensional echocardiographic assessments of left ventricular area and length recorded just before anesthesia induction. Anesthesia was induced by inhalation of increasing inspired concentrations of halothane or isoflurane in oxygen using a pediatric circle system and mask. During controlled ventilation, halothane and isoflurane concentrations were adjusted to maintain 1.0 MAC and then 1.5 MAC (corrected for age), and echocardiographic and hemodynamic measurements were repeated. A final cardiovascular measurement was recorded after intravenous administration of 0.02 mg/kg of atropine. All measurements were completed before tracheal intubation and the start of elective surgery. In neonates, 1.0 MAC concentrations of halothane and isoflurane decreased cardiac output (74% +/- 16%), stroke volume (75% +/- 15%), and ejection fraction (76% +/- 15%) similarly from awake levels. Decreases in cardiac output, stroke volume, and ejection fraction with halothane and isoflurane were significantly larger at 1.5 MAC (approximately 35% decreases from awake values) than at 1.0 MAC. Heart rate decreased significantly during 1.5 MAC halothane anesthesia (94% +/- 4%) but remained unchanged during isoflurane anesthesia. In infants, 1.0 MAC halothane and isoflurane decreased cardiac output (83% +/- 12%), stroke volume (78% +/- 12%), and ejection fraction (74% +/- 12%) when compared with awake measures.(ABSTRACT TRUNCATED AT 250 WORDS)     

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 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.     

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)     

Hemodynamic and organ blood flow responses to halothane and sevoflurane anesthesia during spontaneous ventilation.

This study compared systemic hemodynamic and organ blood flow responses to equipotent concentrations of halothane and sevoflurane during spontaneous ventilation in the rat. The MAC values for halothane and sevoflurane were determined. Cardiac output and organ blood flows were measured using radiolabeled microspheres. Measurements were obtained in awake rats (control values) and at 1.0 MAC halothane or sevoflurane. The MAC values (mean +/- SEM) for halothane and sevoflurane were 1.10% +/- 0.05% and 2.40% +/- 0.05%, respectively. The PaCO2 increased to a similar extent in both groups compared with control values. During halothane anesthesia, heart rate decreased by 12% (P < 0.01), cardiac index by 26% (P < 0.01), and mean arterial blood pressure by 18% (P < 0.01) compared with control values. Stroke volume index and systemic vascular resistance did not change. During sevoflurane anesthesia, hemodynamic variables remained unchanged compared with control values. Coronary blood flow decreased by 21% (P < 0.01) and renal blood flow by 18% (P < 0.01) at 1.0 MAC halothane, whereas both remained unchanged at 1.0 MAC sevoflurane. Cerebral blood flow increased to a greater extent with halothane (63%; P < 0.01) than with sevoflurane (35%; P < 0.05). During halothane anesthesia, hepatic arterial blood flow increased by 48% (P < 0.01), whereas portal tributary blood flow decreased by 28% (P < 0.01). During sevoflurane anesthesia, hepatic arterial blood flow increased by 70% (P < 0.01) without a concomitant reduction in portal tributary blood flow. Total liver blood flow decreased only with halothane (16%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral autoregulation in awake versus isoflurane-anesthetized rats

We evaluated regional cerebral and spinal cord blood flow in rats during isoflurane anesthesia. Tissue blood flow was measured in cerebral cortex, subcortex, midbrain, and spinal cord using radioactive microspheres. Blood flow autoregulation was measured within the following arterial blood pressure ranges (mm Hg): 1 = less than 50, 2 = 50-90, 3 = 90-130, 4 = 130-170, 5 = greater than 170. Arterial blood pressure was increased using phenylephrine infusion and decreased with ganglionic blockade and hemorrhage. Three treatment groups were studied: 1 = awake control, 2 = 1.0 minimum alveolar anesthetic concentration (MAC) isoflurane, 3 = 2.0 MAC isoflurane. Autoregulation was seen in awake rats from 50 to 170 mm Hg in all tissues. The autoregulatory coefficient (change in blood flow/change in blood pressure) was increased in midbrain and spinal cord during 1.0 MAC isoflurane and in all tissues during 2.0 MAC isoflurane (P less than 0.05). Within the arterial blood pressure range of 90-130 mm Hg, isoflurane produced the following changes in tissue blood flow (percent of awake control): 1.0 MAC isoflurane: cortex = 87% +/- 8% (P greater than 0.30), subcortex = 124% +/- 11% (P greater than 0.05), midbrain = 263% +/- 20% (P less than 0.001), spinal cord = 278% +/- 19% (P less than 0.001); 2.0 MAC isoflurane: cortex = 137% +/- 13% (P less than 0.05), subcortex = 272% +/- 24% (P less than 0.001), midbrain = 510% +/- 53% (P less than 0.001), spinal cord = 535% +/- 50% (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Sevoflurane decreases bispectral index values more than does halothane at equal MAC multiples

At the minimum alveolar concentration (MAC) of inhaled anesthetics, 50% of subjects move in response to noxious stimulation. Similarly, at MAC-awake, 50% of subjects respond appropriately to command. The bispectral index (BIS) nominally measures the effect of anesthetics on wakefulness or consciousness. We postulated that the use of halothane with a larger MAC-awake/MAC ratio than sevoflurane would produce higher BIS values at comparable levels of MAC. We studied 33 unpremedicated patients anesthetized by inhalation, 18 with sevoflurane and 15 with halothane. We measured BIS before and during anesthesia at 1 MAC, both before and after tracheal intubation facilitated by fentanyl and rocuronium and then at 1.5 MAC. BIS measurements were made after meeting steady-state conditions. No surgery was performed during this study. BIS values in awake patients did not differ between the sevoflurane and halothane groups (96 +/- 2 and 96 +/- 2, mean +/- sd, respectively). At 1 MAC without and with neuromuscular blockade and at 1.5 MAC, BIS values for patients anesthetized with halothane (54 +/- 7, 56 +/- 7, and 49 +/- 7, respectively) exceeded those for patients anesthetized with sevoflurane (34 +/- 6, 34 +/- 6, and 29 +/- 5, respectively) (P < 0.0001). This finding adds to other evidence indicating that BIS is drug specific.     

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.     

The anticonvulsant effects of volatile anesthetics on lidocaine-induced seizures in cats

Large concentrations of sevoflurane and isoflurane, but not halothane, induce spikes in the electroencephalogram. To elucidate whether these proconvulsant effects affect lidocaine-induced seizures, we compared the effects of sevoflurane, isoflurane, and halothane in cats. Fifty animals were allocated to 1 of 10 groups: 70% nitrous oxide (N2O), 0.6 minimum alveolar anesthetic concentration (MAC) + 70% N2O, 1.5 MAC + 70% N2O, and 1.5 MAC of each volatile agent in oxygen. Lidocaine 4 mg x kg(-1) x min(-1) was infused IV under mechanical ventilation with muscle relaxation. Electroencephalogram in the cortex, amygdala, and hippocampus and multiunit activities in the midbrain reticular formation (R-MUA) were recorded. Lidocaine induced spikes first from the amygdala or hippocampus in the 70% N2O and halothane groups and from the cortex in the sevoflurane and isoflurane groups. Lidocaine induced seizures in all cats in the 70% N2O and 0.6 MAC + N2O groups. Seizure occurrence was reduced in the 1.5 MAC + N2O group (P < 0.05 versus 70% N2O). The onset of seizure was delayed in the 0.6 MAC + N2O and 1.5 MAC groups for sevoflurane and isoflurane, but not for halothane, compared with the 70% N2O group (P < 0.05). Lidocaine increased R-MUA with seizure by 130%+/-56% in the 70% N2O group. The increase of R-MUA with seizure was more suppressed in the volatile anesthetic groups than in the 70% N2O group (P < 0.05). In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased. IMPLICATIONS: Increasingly, epidural blockade is combined with general anesthesia to achieve stress-free anesthesia and continuous pain relief in the postoperative period. In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased.     

Comparison of recovery after intermediate duration of anaesthesia with sevoflurane and isoflurane

BACKGROUND: The purpose of this study was to compare recovery from anaesthesia after sevoflurane and isoflurane were administered to children for more than 90 min. METHODS: After parental informed consent and ethical committee approval, children aged between 2 months and 6 years, ASA I or II, were randomly allocated to sevoflurane (n=20) or isoflurane (n=20) groups. Halogenated agents were discontinued following skin closure and patients were ventilated mechanically with 100% oxygen until minimum alveolar concentration (MAC) values awake were obtained (endtidal concentrations 0.6 MAC for sevoflurane and 0.4 MAC for isoflurane). Effective perioperative analgesia was provided by a caudal block. RESULTS: The mean (+/- SD) duration of anaesthesia was 132 +/- 38 min and 139 +/- 49 min for sevoflurane and isoflurane, respectively. Early recovery occurred sooner in the isoflurane group (time to extubation was 16 +/- 7 min and 11 +/- 5 min, P<0.01; Aldrete's score at 0 min was 5.5 +/- 1.5 and 7.4 +/- 1.8, P<0.001, respectively). But the time to be fit for discharge from recovery room was similar at 136 +/- 18 min and 140 +/- 20 min, respectively. CONCLUSIONS: After intermediate duration of anaesthesia administered to children for up to 90 min, isoflurane and sevoflurane allow recovery after approximatively the same lapse of time.     

Solubility of desflurane (I-653), sevoflurane, isoflurane, and halothane in human blood

The blood/gas partition coefficients for the new volatile anesthetic agent desflurane (I-653), sevoflurane, isoflurane, and halothane were determined, simultaneously, in 8 human volunteers to compare the solubilities of these agents in blood. The blood/gas partition coefficient for desflurane [0.49 +/- 0.03 (mean +/- SD)] was smallest, followed by sevoflurane (0.62 +/- 0.04), isoflurane (1.27 +/- 0.06), and halothane (2.46 +/- 0.09). Differences among the anesthetic agents were significant (P less than 0.001). The results of this study confirm that among these agents the solubility of desflurane in human blood is the smallest. The results suggest that the washin and washout of desflurane will be more rapid than that of sevoflurane, isoflurane, and halothane, and the washin and washout of sevoflurane will be more rapid than that of isoflurane and halothane.     

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).     

The comparative cardiovascular effects of sevoflurane with halothane and isoflurane

Using closed chest dogs, the cardiovascular effects of sevoflurane were compared with those of halothane and isoflurane in equipotent doses of 1.0, 1.5, 2.0, 2.5 and 3.0 MAC. They were evaluated by the changes of arterial blood pressure, central venous pressure, pulmonary artery pressure, maximum rate of left ventricular pressure rise (LV dp/dt), cardiac output and coronary sinus blood flow. The suppression of left cardiac function by sevoflurane was less than that of halothane, but was greater than that of isoflurane. Heart rate, systemic vascular resistance with sevoflurane were slightly lower than that of isoflurance. The coronary sinus blood flows with sevoflurane and isoflurane were significantly (P < 0.05 at 1.0 MAC, P < 0.005 at 2.0 MAC) higher than halothane. There was no significant difference on coronary sinus flow between sevoflurane and isoflurane. The depth of anesthesia could be quickly changed by adjustment of inspired sevoflurane concentration in comparison with the other two anesthetics.(Kazama T, Ikeda K: The comparative cardiovascular effects of sevoflurane with halothane and isoflurane. J Anesth 2: 63–68, 1988)     

Comparison of the effects of sevoflurane, isoflurane and halothane on indocyanine green clearance

We have examined the effects of inhalation anaesthetics on indocyaninegreen (ICG) clearance, as an index of hepatic function, in patientsundergoing elective surgery. Recently, a new method has beendeveloped to measure in real-time the disappearance rate ofICG from plasma. This method eliminates the multiple samplingand delay of the conventional ICG test. ICG clearance is displayedas two indices: K (ICG disappearance rate) and R₁₅ (ICG retentionrate 15 min after injection of ICG 0.5 mg kg^–1 This measurementwas performed in patients before and after 1 MAC of sevoflurane(n = 6), 2 MAC of sevoflurane (n = 6), 1 MAC of isoflurane (n= 6), 2 MAC of isoflurane (n = 6), 1 MAC of halothane (n = 6)or 2 MAC of halothane (n = 6) without surgical stress. Althoughmean arterial pressure decreased significantly at 1 and 2 MACof sevoflurane, 2 MAC of halothane, and 1 and 2 MAC of isoflurane,ICG clearance was maintained at awake levels, except at 2 MACof halothane (K mean - 33 (SEM 3)%, R = + 90 (3)% from awakevalues). We conclude that sevoflurane and isoflurane have amore favourable effect on liver circulation than halothane.      

Effects of anesthesia on norepinephrine kinetics. Comparison of propofol and halothane anesthesia in dogs

Alteration of sympathetic function is a major determinant of the cardiovascular effects of anesthetic agents. Plasma norepinephrine (NE) concentrations are determined not only by the rate of NE release from sympathetic nerves but also by NE clearance rate. Therefore, NE concentration in plasma may be an inadequate index of sympathetic activity. We used an isotope dilution technique to investigate the effects of halothane and propofol anesthesia on NE kinetics. A relationship of NE kinetics to halothane dose was determined in six dogs. Halothane 1.0 MAC reduced plasma NE concentration by 35 +/- 9% versus awake (P less than 0.05). This was due to a reduction of 52 +/- 9% in NE spillover (P less than 0.05) accompanied by a reduction of 27 +/- 5% in NE clearance (P less than 0.005). The clearance changes were dose-dependent: reductions were 34 +/- 4% at 1.5 MAC (P less than 0.05 vs. 1.0 MAC) and 45 +/- 5% at 2.0 MAC (P less than 0.05 vs. 1.5 MAC). Six dogs were studied with a single halothane dose (1.0 MAC) and NE concentration, spillover, and clearance were found to be stable over a period of 5.5 h of anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of halothane, isoflurane, or sufentanil on the hypertensive response to cerebellar retraction during posterior fossa surgery

The blood pressure (BP) response to cerebellar retraction during microvascular decompression of the fifth cranial nerve was investigated in 26 ASA physical status 2 or 3 patients with trigeminal neuralgia. One surgeon performed all operations. To determine the effect of three anesthetic techniques on the BP response, patients were randomly assigned to receive halothane, isoflurane, or sufentanil in sufficient doses with 60% nitrous oxide to achieve a precerebellar retraction systolic BP that was 10-20% below the average ward systolic BP (as per standard clinical practice). The resultant doses were halothane 1.65 +/- 0.27 (mean +/- SD) MAC, isoflurane 1.56 +/- 0.17 MAC (P greater than 0.05), and sufentanil 2.7 micrograms/kg (MAC values include 0.6 MAC contribution from 60% nitrous oxide). In all patients BP increased during the cerebellar retractor placement period compared with the preretractor placement period (P less than 0.05). The peak increase in systolic BP in response to cerebellar retraction was 17 +/- 6 mmHg for halothane, 38 +/- 20 mmHg for isoflurane, and 26 +/- 19 mmHg for sufentanil. The difference between halothane and isoflurane was significant (P less than 0.05). Mean and diastolic BP showed similar significant differences. The authors conclude that halothane attenuates the hypertensive response to cerebellar retraction more than isoflurane when administered in approximately 1.6 MAC concentrations (MAC value includes contribution from nitrous oxide).     

The effect of sevoflurane and isoflurane anesthesia on interictal spike activity among patients with refractory epilepsy.

The electrophysiologic effects of sevoflurane are not well characterized in humans. Among patients with refractory epilepsy, this study compared 1) electroencephalographic (EEG) interictal spike activity during wakefulness and sevoflurane anesthesia, and 2) electrocorticographically (ECoG) recorded interictal spike activity during sevoflurane and isoflurane anesthesia. We studied 12 patients undergoing insertion of subdural electrodes. Before commencing anesthesia, awake (baseline) EEG recordings were obtained. After inhaled induction, EEG interictal spike activity was evaluated during stable, normocapnic, and hypocapnic (Paco2 = 28-30 mm Hg), sevoflurane anesthesia administered at 1.5 times the minimum alveolar anesthetic concentration (1.5 MAC). Immediately after surgery, ECoG recordings were obtained from subdural electrodes during 1) 1.5 MAC isoflurane, 2) 0.3 MAC isoflurane, and 3) 1.5 MAC sevoflurane anesthesia. EEG spike frequency increased in all patients during sevoflurane anesthesia compared with awake recordings (P = 0.002). Compared with 0.3 MAC isoflurane anesthesia, ECoG interictal spike frequency was higher in all patients during 1.5 MAC sevoflurane anesthesia (P = 0.004) and in 8 of 10 patients during 1.5 MAC isoflurane anesthesia (P = 0.016). Under sufficiently rigorous conditions, both sevoflurane and isoflurane can provoke interictal spike activity at near burst-suppression doses. This property is more prominent with sevoflurane than isoflurane. IMPLICATIONS: The results of this study suggest that the capacity to modulate neuroexcitability is a dose-dependent feature of volatile anesthetics that is manifested most prominently at near burst-suppression doses (i.e., 1.5 times the minimum alveolar anesthetic concentration) and is minimal or absent at low doses.     

Protective effects of volatile agents against methacholine-induced bronchoconstriction in rats

BACKGROUND: The protective properties of common volatile agents against generalized lung constriction have previously been addressed only via estimations of parameters that combine airway and tissue mechanics. Their effectiveness in preventing airway constriction have not been compared systematically. Therefore, the authors investigated the abilities of halothane, isoflurane, sevoflurane, and desflurane to provide protection against airway constriction induced by methacholine. METHODS: Low-frequency pulmonary impedance data were collected in open-chest rats under baseline conditions and during three consecutive intravenous infusions of methacholine (32 microg x kg(-1) x min(-1)) while the animals were anesthetized with intravenous pentobarbital (control group). Methacholine challenges were performed in four other groups of rats, first during intravenous anesthesia and then repeated during the inhalation of halothane, isoflurane, sevoflurane, or desflurane at concentrations of 1 and 2 minimum alveolar concentration (MAC). Airway resistance and inertance, parenchymal damping, and elastance were estimated from the impedance data by model fitting. RESULTS: The methacholine-induced increases in airway resistance during intravenous pentobarbital anesthesia (204 +/- 53%) were markedly and significantly (P < 0.005) reduced by 1-MAC doses of halothane (80 +/- 48%), isoflurane (112 +/- 59%), sevoflurane (68 +/- 34%), and desflurane (96 +/- 34%), with no significant difference between the gases applied. Increasing the concentration to 2 MAC did not lead to any significant further protection against the increase in airway resistance. CONCLUSIONS: These data demonstrate that isoflurane, sevoflurane, and desflurane are as effective as the widely accepted halothane in protecting against methacholine-induced airway constriction.