Hepatic oxygen supply-uptake relationship and metabolism during anesthesia in miniature pigs

The study evaluated the effects of different anesthetics on the hepatic oxygen supply-demand relationship and hepatic lactate uptake (HLu). Miniature pigs (n = 33), weighing 20-31 kg, were divided into five groups and accordingly anesthetized with halothane, isoflurane, enflurane (0.9%, 1.5%, and 2.2% end-expired concentrations, respectively), fentanyl (100 micrograms/kg iv bolus followed by a continuous infusion of 50 micrograms.kg-1.h-1), or sodium pentobarbital (30 mg/kg iv bolus followed by a continuous infusion at a rate of 1-2 mg.kg-1.h-1). The surgical preparation allowed the authors to induce a stepwise decrease in hepatic blood supply without congestion in the preportal tissues. Prior to induced hepatic hypoperfusion, the values of hepatic oxygen delivery (HDO2) were the greatest in the isoflurane and fentanyl groups and the smallest in the halothane group, while the values of hepatic oxygen uptake (HVO2) were the smallest in the halothane group without differences among the other four groups. During stepwise decrease in hepatic blood and oxygen supply, HLu started to decrease at higher values of hepatic oxygen delivery in the fentanyl group (HDO2 = 10 mlO2.min-1.100 g-1) than in all others (HDO2 = 6-7 mlO2.min-1.100 g-1). At values of HDO2 equal to 2-3 mlO2.min-1.100 g-1, the values of HLu became negative, signifying that the liver began to release rather than to metabolize lactate. There was a linear relationship between the values of HDO2 and hepatic venous oxygen tension or saturation (r = 0.96; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic blood flow in humans during isoflurane-N2O and halothane-N2O anesthesia

Hepatic blood flow (HBF) (assessed by plasma clearance and hepatic extraction of indocyanine green), cardiac index, and hepatic venous oxygen saturation were measured in patients before and after induction of anesthesia with thiopental, fentanyl, and N2O, and again during halothane (1 MAC)-N2O (n = 5) or isoflurane (1 MAC)-N2O (n = 6) anesthesia before the start of surgery. Induction of anesthesia decreased HBF and cardiac index. Before administration of volatile anesthetics, both groups had similar values of HBF, cardiac index, and hepatic venous oxygen saturation. During anesthesia cardiac index remained stable in both groups, whereas HBF increased significantly with isoflurane but did not change significantly with halothane. Hepatic venous oxygen saturation was also significantly greater during isoflurane than during halothane anesthesia. We conclude that isoflurane increases HBF in anesthetized patients and is associated with a higher hepatic venous oxygen saturation than is halothane.     

Effect of oxygen concentration, hyperthermia, and choice of vendor on anesthetic-induced hepatic injury in rats

Although hypoxic rats exposed to anesthetics may develop hepatic injury, divergent results have been obtained. These discrepancies might be due to different levels of hypoxia, hypothermia, or choice of vendor. Male Sprague-Dawley rats purchased from Zivic-Miller were pretreated with phenobarbital for 4 days. After 24 h without phenobarbital, they were exposed to 2 h of hypoxia and halothane, enflurane, isoflurane, thiopental, or fentanyl. Rectal temperature was kept between 36.5 degrees C and 38.5 degrees C. All agents given in 10% oxygen produced more hepatic injury than did control conditions (exposure to 10% oxygen alone) (P less than 0.01). Only halothane given in 12% and 14% oxygen produced hepatic injury. No agent given in 20% or 100% oxygen demonstrated hepatotoxicity. In a separate study, rectal temperatures were kept between 32 degrees C and 34 degrees C during 2 h of exposure to 0.3 MAC halothane, enflurane, or isoflurane in 10% oxygen. Hypothermia prevented hepatotoxicity by enflurane and isoflurane, but not by halothane. Finally, although livers of rats obtained from Zivic-Miller were injured, specific pathogen-free rats from Charles River were not injured or were less injured by enflurane, thiopental, or fentanyl. Apparently, minor changes in experimental conditions can substantially affect results; hepatic hypoxia per se, anesthetic metabolism (especially that of halothane), and perhaps anesthesia itself may produce hepatic injury.     

Celiac plexus block does not alter hepatic injury in rats

We previously demonstrated that upper abdominal surgery on rats pretreated with phenobarbital and anesthetized with halothane caused centrilobular necrosis of the liver, which may be secondary to hepatic hypoxia induced by vasoconstriction. This study examined the possibility that celiac plexus blockade might decrease the degree of injury seen in the surgical model. Rats, pretreated with phenobarbital, were anesthetized with halothane, enflurane, isoflurane, or fentanyl with 100% oxygen. At the start of the hepatic artery dissection, the celiac plexus was blocked by injection of bupivacaine. Subsequently, the rat livers were evaluated for presence and degree of centrilobular necrosis. Animals anesthetized with halothane or fentanyl had a significantly greater incidence of centrilobular necrosis than controls (rats pretreated with phenobarbital who received no anesthesia or surgery). Hepatic injury in rats anesthetized with isoflurane or enflurane did not differ from that in controls. We conclude that celiac plexus blockade with bupivacaine provides no protection against hepatic necrosis in this model.     

Effects of halothane, isoflurane, enflurane, thiopental, and fentanyl on blood gas values in rats exposed to hypoxia

In rats pretreated with phenobarbital breathing 10% oxygen, subanesthetic doses of halothane, isoflurane, enflurane, thiopental, and fentanyl caused hepatic injury. Because hypoxia per se can produce such injury, we hypothesized that the anesthetic-induced injury resulted from increased hypoxemia secondary to respiratory depression. Male Sprague-Dawley rats were pretreated with phenobarbital; half of the rats were fed and the other half were deprived of food for the 24 h before study. Isoflurane anesthesia was given for the placement of a catheter into the femoral artery. After 1 h of recovery, the rats were exposed to 10% oxygen. Control samples were obtained and halothane, isoflurane, enflurane, thiopental, or fentanyl was administered. Rats given food had higher PaCO2 and lower pH values than starved rats. Also, arterial oxygen saturation (SaO2) tended to be lower in rats given food. At concentrations of 0.15-0.2 MAC or higher, halothane, isoflurane, and enflurane slightly increased PaCO2 values relative to values for a control group exposed only to hypoxia. However, SaO2 and PaO2 did not show significant drug-induced changes. Fentanyl transiently decreased PaO2 and SaO2. Thiopental caused no changes. Thus, we conclude that subanesthetic doses of anesthetics may depress the ventilatory response to hypoxia but that this depression is inconsistent and appears to be too small to cause hepatic damage.     

Hepatic energy charge and adenine nucleotide status in rats anesthetized with halothane, isoflurane or enflurane

Background: Volatile anesthetics are known to have varying effects on hepatic oxygen supply in vivo and have been shown to depress hepatic mitochondrial respiration and so energy charge in vitro. However, the effect of halothane, isoflurane and enflurane on hepatic adenine nucleotide status in viuo has not been evaluated.
Methods: Ninety male rats were exposed to 40% oxygen (n=22) or 40% oxygen in equipotent (1 MAC) concentrations of halothane (1%) (n=23), isoflurane (1.4%) (n=22) or enflurane (2%) (n=23) for 2 hours. All animals were then administered intraperitoneal pentobarbital and anesthesia continued and laparotomy was performed. A liver biopsy was taken for determination of hepatocellular adenosine-5-triphosphate (ATP), adenosine-5-diphosphate (ADP) and adenosine-5-monophosphate (AMP) and computation of energy charge (EC) from ((ATP+1/2 ADP)+(ATP+ADP+AMP)) and total ade nine nucleotides (TAN) from (ATP+ADP+AMP). After the biopsy the aorta was cannulated for blood sampling.
Results: Rats in each group were similar in weight, as well as acid base and blood gas status just after liver biopsy. Hepatic energy charge, ATP, ADP, AMP, and TAN levels were not different in animals receiving either halothane, isoflurane or enflurane when compared with those receiving only oxygen.
Conclusions: One MAC of anesthesia for a period of 2 hours with the described volatile anesthetic agents did not affect adenine nucleotide status in viuo in rats.     

Suppression of motor evoked potentials by inhalation anesthetics

The purpose of this study was to record evoked action potentials from forearm muscles in response to single-shock supramaximal electrical stimulation of motor cortex in room air and under different concentrations (0.5-1.5%) of isoflurane, enflurane, and halothane anesthesia in rats. Anesthesia was induced with a mixture of fentanyl and droperiodol, which was then followed by 10-min inhalation of each gas anesthetic under controlled ventilation. Increasing concentrations of isoflurane (n = 12) caused a progressive increase in onset latency and a decrease in peak-to-peak amplitude and duration. Similar increases in latency and decreases in amplitude and duration occurred under enflurane (n = 10) and halothane (n = 10) anesthesia. The three anesthetics caused a significant latency increase over baseline (room air) values for concentrations from 0.5 to 1.5% (p < 0.01). The amplitude and duration of muscle responses under all three volatile anesthetics at 0.5-1.5% concentrations were significantly lower than baseline (p < 0.01). Isoflurane, enflurane, and halothane anesthesia significantly altered the muscle response evoked by motor cortex stimulation in experimental animals.     

Alterations in influenza virus pulmonary pathology induced by diethyl ether, halothane, enflurane, and pentobarbital anesthesia in mice

Three-week-old CD-1 mice infected with the PR-8 (mouse-adapted) strain of influenza virus while exposed to enflurane demonstrated a decrease in virus titers from the lungs of infected animals, less abnormality of lung histology, and an increase in survival in animals as compared with those receiving the other anesthetics tested. Greater than 90% mortality occurred in groups of mice which inhaled aerosolized virus and received no anesthesia, pentobarbital, diethyl ether, or halothane anesthesia 96 h following infection. Infected mice anesthetized with enflurane 96 h post-infection had significantly lower mortality rate (68%) when compared with the other groups. Halothane-anesthetized mice receiving intranasal influenza virus during anesthesia demonstrated increased survival and a delay in the mean day of death when compared with animals receiving either diethyl ether of pentobarbital anesthesia. Animals receiving enflurane during virus inoculation had an even lower mortality rate and a later mean day of death when compared with infected animals receiving day of the other three anesthetics. Examination of lungs from animals infected during anesthesia demonstrated influenza virus titers significantly less in the animals that received enflurane anesthesia when compared with the other groups. Histologic sections of lungs revealed extensive spread of the disease process into the alveoli and interstitium of the lungs of animals infected while receiving pentobarbital or diethyl ether anesthesia. Animals infected during halothane demonstrated pathologic characteristics similar to pentobarbital- and diethyl-ether-treated groups; however, the changes were not as extensive. Mice infected during exposure to enflurane revealed only a mild bronchopneumonia.     

Hepatolobectomy-induced depression of hepatic circulation and metabolism in the dog is counteracted by isoflurane, but not by halothane

BACKGROUND: The effects of isoflurane and halothane anesthesia on hepatic circulation and oxygen metabolism during hepatolobectomy were investigated in the dog, in an attempt to assess which of the anesthetics was the better one for hepatic resection. METHODS: Mongrel dogs (n=24) were divided into two groups and accordingly anesthetized with isoflurane (n=12) or halothane (n = 12). Each test anesthetic was administered in air. Electromagnetic flowmeters were used to measure hepatic arterial and portal venous blood flows 1) before the inhalation of each anesthetic (baseline); 2) 1 h inhalation of 1.5 MAC (minimum alveolar concentration) of each anesthetic; and 3) 1 h after hepatolobectomy with each anesthesia. Measurements of systemic hemodynamics, blood gas tensions, and the arterial ketone body ratio were made at the same time. RESULTS: Isoflurane maintained portal venous, hepatic arterial and total hepatic blood flows better than halothane anesthesia before and after hepatolobectomy. With halothane anesthesia, hepatolobectomy decreased prominently hepatic arterial blood flow. Hepatic arterial and mesenteric vascular resistance increased in the halothane group, but remained constant in the isoflurane group after hepatolobectomy. Hepatic oxygen delivery was significantly suppressed in the halothane group, but did not change in the isoflurane group. No significant difference was found in hepatic oxygen consumption between the two groups, but the arterial ketone body ratio decreased significantly only in the halothane group before and after hepatolobectomy. CONCLUSION: The present data indicate that isoflurane has less adverse effect than halothane anesthesia on hepatic circulation, oxygen delivery and energy charge in hepatolobectomy cases.     

Effects of halothane and fentanyl on the rate of CSF production in dogs

Using the open ventriculocisternal perfusion method, the rate of cerebrospinal fluid (CSF) production was examined in dogs anesthetized with either halothane (0.8%) or fentanyl (3.0 micrograms/kg/min for 20 min, then 0.2 micrograms/kg/min, intravenously), and nitrous oxide (60-70%) in oxygen. Halothane decreased the mean rate of CSF production from 0.047 +/- 0.006 ml/min (mean +/- SEM) in controls to 0.033 +/- 0.005 ml/min. This effect persisted throughout 3.0-3.5 h of anesthesia. When the expired concentration of halothane was decreased from 0.8% to less than 0.1%, the mean rate of CSF production returned to control values within 45-50 min. Fentanyl produced no change in the mean rate of CSF production compared to controls. These data suggest that increased CSF volume does not contribute to increased intracranial pressure during prolonged halothane anesthesia. In patients at risk for increased intracranial pressure due to increased CSF volume, either halothane or fentanyl may be preferable to anesthetics that may increase CSF production, e.g., enflurane.     

Hepatic oxygen supply during halothane or isoflurane anesthesia in guinea pigs

The present study was designed to determine changes in hepatic oxygen supply in guinea pigs during halothane or isoflurane anesthesia. Twenty-seven guinea pigs were randomly divided into three equal groups: control (no anesthesia) group, and animals anesthetized with halothane or isoflurane to decrease mean arterial pressure (MAP) by 50%. Hepatic arterial blood flow (HABF) and portal blood flow (PBF), as well as arterial and portal venous blood oxygen content, were determined in awake animals (stage I, baseline values), and during anesthesia (stage II). HABF was found to be extremely low (0.04 ml.min-1.g-1) during both stages of observation in the control (no anesthesia) group, as well as during stage I (awake) in animals treated with halothane or isoflurane. Equal degrees of arterial hypotension during halothane and isoflurane anesthesia were accompanied by decreased HABF during halothane (37%), but no significant change in HABF during isoflurane anesthesia. PBF decreased significantly in both experimental groups; however, the decrease was more prominent during halothane than during isoflurane anesthesia (57% vs. 23%). The observed hepatic circulatory changes led to a 65% decrease in hepatic oxygen delivery during halothane, but only a 34% decrease during isoflurane anesthesia. The present study does not exclude the possibility that liver damage in the guinea pig model is related to the reductive metabolism of halothane or any other mechanism. However, the extremely low HABF and a prominent reduction in both HABF and PBF during halothane anesthesia may be responsible for hepatic damage observed in the guinea pig model.     

Isoflurane when compared to enflurane and halothane decreases the frequency of cerebral ischemia during carotid endarterectomy

Data from the records of patients who underwent 2223 carotid endarterectomies at the Mayo Clinic between January 1, 1972, and December 31, 1985, were abstracted to compare the effects of isoflurane, enflurane, and halothane on the critical cerebral blood flow (CBF) (i.e., the CBF below which the majority of patients develop EEG ischemic changes within 3 min of carotid occlusion), the incidence of EEG ischemic changes, and the neurologic outcome. In a total of 2196 of these procedures, the patient received one of the three volatile anesthetics and, in 2010 of these, both the EEG and the CBF were monitored. Chronologically, halothane was the primary agent from 1972-1974; enflurane progressively replaced halothane during 1975-1981; and isoflurane was used almost exclusively since 1982. This analysis confirmed a previous study that the critical CBF during isoflurane anesthesia (703 procedures) was approximately 10 ml X 100 g-1 X min-1, as contrasted to that of approximately 20 ml X 100 g-1 X min-1 during halothane anesthesia (467 procedures). This analysis also established that the critical CBF during enflurane anesthesia (840 procedures) was approximately 15 ml X 100 g-1 X min-1. The incidence of EEG ischemic changes was significantly less (P less than 0.001) during isoflurane anesthesia (18%) than during either enflurane (26%) or halothane (25%) anesthesia. This difference occurred despite the fact that the preoperative risk status was greater in the patients given isoflurane. There was no difference in neurologic outcome between the three anesthetics, and none was expected, since all patients with EEG changes were immediately shunted, if possible.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic circulation during surgical stress and anesthesia with halothane, isoflurane, or fentanyl

Hepatic blood flow and the oxygen supply/uptake relation were studied in 19 miniature pigs using labeled microspheres. Changes in hepatic arterial blood flow and portal blood flow, as well as total hepatic blood flow during halothane anesthesia were more closely associated with changes in mean arterial pressure (MAP) and cardiac output than during anesthesia with isoflurane or fentanyl. Halothane or isoflurane administered in concentrations that decreased MAP by approximately 30% were accompanied by decreases in hepatic oxygen delivery (DO2th) averaging 46% during halothane and 31% during isoflurane anesthesia and parallel decreases in hepatic blood flow. In concentrations that decreased MAP by 50%, halothane and isoflurane decreased DO2th 61 and 37%, respectively. DO2th was maintained (statistically insignificant, 23% increase) during both doses of fentanyl administered (20 micrograms/kg followed by 0.17 microgram . kg-1 . min-1, and 50 micrograms/kg followed by 0.42 microgram . kg-1 . min-1). Hepatic oxygen uptake increased 50% during fentanyl and was maintained at baseline levels during both doses of halothane and isoflurane anesthesia. Oxygen content in hepatic venous blood was maintained at baseline levels during fentanyl and isoflurane administration and was decreased by both concentrations of halothane anesthesia. The hepatic oxygen supply demand ratio was maintained at baseline levels after both doses of fentanyl and during isoflurane administered in a concentration that decreased blood pressure 30%; the ratio decreased during isoflurane administered in a concentration decreasing blood pressure by 50% and during both doses of halothane anesthesia.(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)     

Effect of Different Anesthetics on the Pharmacokinetics and Pharmacodynamics of Pancuronium in the Cat

To investigate the effect of different anesthetics on the pharmacokinetics and pharmacodynamics of pancuronium, 120 microgram/kg i.v., cats were anesthetized with either pentobarbital (N = 4), ketamine (N = 4), enflurane (N = 5), or halothane (N = 5). A longer onset time and duration of neuromuscular blockade occurred during enflurane and halothane anesthesia. The apparent elimination half-life was longer and the total voluem of distribution at steady state larger during halothane anesthesia. The plasma concentration of pancuronium required for neuromuscular blockades was less during enflurane than during the other three anesthetics. We conclude that inhalation anesthetics may prolong a neuromuscular blockade by altering both the pharmacokinetics and pharmacodynamics of pancuronium.     

Pipecuronium-induced neuromuscular blockade during nitrous oxide-fentanyl, enflurane, isoflurane, and halothane anesthesia in surgical patients.

This study was designed to determine the capacity of several anesthetics to augment pipecuronium neuromuscular blockade. The potency of pipecuronium was determined with single-bolus administration of 20-50 micrograms/kg in 160 patients. Patients were anesthetized with N2O/O2 (60:40) supplemented with fentanyl (4-5 micrograms/kg), halothane (0.8%), isoflurane (1.2%), or enflurane (1.7%). Neuromuscular blockade was measured by an acceleration-responsive transducer (the Accelograph, Biometer International, Odense, Denmark). Responses were defined in terms of percent depression in first-twitch height and train-of-four response, and the dose-response curves were constructed after probit transformation of the responses. The dose-response curves were found to be parallel for both first twitch height and train-of-four responses. The dose-response lines for the enflurane and isoflurane groups were displaced significantly (P less than 0.01) to the left of the line for the fentanyl-N2O group. The calculated doses producing 50% depression of first twitch height were 21.9, 21.2, 18.9, and 17.8 micrograms/kg for the N2O-fentanyl, halothane, isoflurane, and enflurane groups, respectively. Corresponding calculated doses for 50% depression of train-of-four response were significantly smaller (15.5, 14.4, 13.7, 11.9 micrograms/kg, respectively). The enhancing effects of the volatile anesthetics were reflected by significant prolongation of the clinical duration of neuromuscular blockade by pipecuronium. It is concluded that the potency of pipecuronium is enhanced more by enflurane and isoflurane than halothane or fentanyl-N2O anesthesia.     

Narcotics decrease heart rate during inhalational anesthesia

We determined the heart rate (HR) response to enflurane, halothane, and isoflurane and the effects of narcotics on this response in 81 healthy patients scheduled for elective surgery. Patients were randomly assigned to one of six treatment groups: one of the three anesthetics (approximately 0.9 MAC) in 60% nitrous oxide, and either 0.15 mg/kg of intramuscular morphine 30-60 min before induction or 1 microgram/kg of IV fentanyl 10 min after skin incision. All patients received diazepam, 10 mg orally, 60-90 min before anesthesia, a rapid sequence intravenous induction, and mechanically controlled ventilation. During inhalational anesthesia and the first 10 min of surgery, no significant change in HR occurred in any group (compared to the preinduction HR), although patients given morphine premedication tended to have a decreased HR and those not given morphine premedication tended to have an increased HR. These trends partially account for significant differences that emerged between groups after induction of anesthesia. Patients given morphine premedication and halothane had lower HR (64 +/- 3 SEM) than patients given isoflurane (80 +/- 3) or enflurane (84 +/- 3) and no morphine premedication. Patients anesthetized with enflurane and morphine premedication had lower HR (71 +/- 3) than patients given enflurane without morphine premedication. Administration of fentanyl 10 min after incision (these patients had received no morphine) significantly decreased HR in the presence of any of the vapors. We conclude that inhalational anesthetics used in the clinical setting we employed do not significantly increase heart rate, and that prior administration of morphine or concurrent administration of fentanyl may significantly decrease HR.     

Mean equipotent blood pressure-lowering concentrations of halothane, isoflurane and enflurane during balanced anesthesia differ from conventional MAC-values]

Balanced anesthesia is a technique that allows control of blood pressure in patients with coronary artery disease. In order to evaluate the relative requirements of volatile anesthetics during basic opioid analgesia, 51 patients with unimpaired left ventricular function who were undergoing coronary artery bypass grafting during balanced anesthesia were investigated. They were randomly assigned to three groups, i.e. halothane (H), isoflurane (I), and enflurane (E). Permanent medications were maintained up to 12 h preoperatively. After premedication with flunitrazepam, promethazine and piritramide, anesthesia was induced with 7 micrograms/kg fentanyl, 0.3 mg/kg etomidate, and 0.1 mg/kg pancuronium and continued with fentanyl infusion (0.1 microgram/kg-1 min-1). Volatile anesthetics were applied in oxygen/air and adjusted to keep the mean arterial blood pressure within +/- 20% of the preoperative value. End-expiratory concentrations of volatile anesthetics were measured (Capnomac, DATEX) and averaged over time. The mean ages of the patients in the different groups were 60 +/- 7.6 years (H), 59 +/- 7.1 years (I), and 60 +/- 6.9 years (E). Four patients in the halothane group, six in the isoflurane group, and five in the enflurane group took beta-blockers preoperatively. The cumulative doses of fentanyl were: H = 0.80 +/- 0.17 mg, I = 0.85 +/- 0.16 mg, and E = 0.83 +/- 0.16 mg at the time of skin incision and H = 1.20 +/- 0.26 mg, I = 1.38 +/- 0.19 mg, and E = 1.24 +/- 0.25 mg at the beginning of extracorporeal circulation.2+ which are possibly the reason for the high O2-MAC value, which may be abolished during balanced anesthesia. However, both the negative inotropic and the vasodilatory effects of enflurane are more likely explanations for the results. It is concluded that 0.5 to 1.0 MAC of halothane, isoflurane, or enflurane used as equipotent components of balanced anesthesia for blood pressure control during aorto-coronary bypass grafting may differ considerably from the conventional MAC concept.     

Effects of volatile anesthetics or fentanyl on hepatic function in cirrhotic rats

Halothane, enflurane, isoflurane, and fentanyl were examined for their potential to exacerbate liver dysfunction in rats with preexisting cirrhosis. Male Wistar rats given sodium phenobarbital for 2 weeks are assigned randomly to two groups. One group (cirrhotic) was exposed by inhalation to carbon tetrachloride (CCl4) in air at weekly intervals for 12 weeks to induce cirrhosis. The other group (noncirrhotic) was handled similarly but received air only. Five weeks after the last exposure to CCl4, cirrhotic and noncirrhotic rats were given three hours of 1 MAC halothane, enflurane, or isoflurane in 50% oxygen, or 350 micrograms fentanyl per kg of body weight and 50% oxygen, or 50% oxygen only. Blood gas tensions and blood glucose levels were measured before, during, and at the end of exposure. Forty-eight hours after exposure, serum chemistries were measured in each rat for comparison with preexposure values. Rats were then killed by CO2 overdose, and liver, kidney, and testis were prepared for microscopic examination. Enflurane, isoflurane, and halothane, but not fentanyl, produced mild respiratory acidosis and no change in serum glucose levels. All anesthetics resulted in a mild but similar degree of acute liver dysfunction as indicated by small increases in SGOT or SGPT in both cirrhotic and noncirrhotic rats. Liver histology revealed mild to moderate portal cirrhosis with fibrosis and well-developed micronodules in rats exposed to CCl4, but no superimposed acute hepatocellular damage was noted. It is concluded that all the anesthetics used in this study were associated with the same minimal degree of postanesthetic hepatic dysfunction and that the dysfunction was similar in both cirrhotic and noncirrhotic rats.     

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)