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)     

Screening for Decreased Renal Function in Taxi Drivers in Tehran,Iran

Introduction. Halogenated anesthetics can cause changes in the variables that modify the cardiac output necessary to maintain renal hemodynamic during hemorrhagic shock and resuscitation. However, halogenated anesthetics seem to protect against renal ischemia-reperfusion injury. In a model of pressure-guided hemorrhagic shock in dogs, we studied the comparative effects of three halogenated anesthetics—halothane, sevoflurane, and isoflurane—at equipotent concentrations on renal responses after resuscitation. Methods. Thirty dogs were anesthetized with 1.0 minimum alveolar anesthetic concentration (MAC) of halothane, sevoflurane, or isoflurane. The dogs were splenectomized and hemorrhaged to hold mean arterial pressure at 40–50 mm Hg over 45 min and then resuscitated with the shed blood volume. Hemodynamic variables were measured at baseline, after 45 min of hemorrhage, and 15 and 60 min after resuscitation. Renal variables were measured at baseline and 15 and 60 min after resuscitation. Results. Hemorrhage induced reductions of mean arterial pressure, filling pressures, and cardiac index (p?<?0.05), without significant differences among groups (p?> 0.05). After 60 min of shed blood replacement, all groups restored hemodynamic and renal variables to the prehemorrhage levels (p?> 0.05), without significant differences among groups (p?> 0.05), with the exception of sodium fractional excretion, the values for which were significantly higher in isoflurane group, in relation to the other groups after 15 min of re-transfusion (p?<?0.05), and renal vascular resistance, the values for which remain lower than baseline in halothane group (p?<?0.05). Conclusions. We conclude that no difference could be detected between choosing equipotent doses of halothane, sevoflurane, or isoflurane in relation to renal variables in dogs submitted to pressure-adjusted hemorrhagic shock and resuscitation.     

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 minimum alveolar concentration (MAC) and hemodynamic effects of halothane, isoflurane, and sevoflurane in newborn swine

To determine the minimum alveolar concentration (MAC) and hemodynamic responses to halothane, isoflurane, and sevoflurane in newborn swine, 36 fasting swine 4-10 days of age were anesthetized with one of the three volatile anesthetics in 100% oxygen. MAC was determined for each swine. Carotid artery and internal jugular catheters were inserted and each swine was allowed to recover for 48 h. After recovery, heart rate (HR), systemic systolic arterial pressure (SAP), and cardiac index (CI) were measured awake and then at 0.5, 1.0, and 1.5 MAC of the designated anesthetic in random sequence. The (mean +/- SD) MAC for halothane was 0.90 +/- 0.12%; the MAC for isoflurane was 1.48 +/- 0.21%; and the MAC for sevoflurane was 2.12 +/- 0.39%. Awake (mean +/- SD) measurements of HR, SAP, and CI did not differ significantly among the three groups. Compared to the awake HR, the mean HR decreased 35% at 1.5 MAC halothane (P less than 0.001), 19% at 1.5 MAC isoflurane (P less than 0.005), and 31% at 1.5 MAC sevoflurane (P less than 0.005). Compared to awake SAP, mean SAP measurements decreased 46% at 1.5 MAC halothane (P less than 0.001), 43% at 1.5 MAC isoflurane (P less than 0.001), and 36% at 1.5 MAC sevoflurane (P less than 0.005). Mean SAP at 1.0 and 1.5 MAC halothane and isoflurane were significantly less than those measured at equipotent concentrations of sevoflurane (P less than 0.005). Compared to awake CI, mean CI measurements decreased 53% at 1.5 MAC halothane (P less than 0.001) and 43% at 1.5 MAC isoflurane (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative coronary vascular reactivity and hemodynamics during halothane and isoflurane anesthesia in swine

To assess the dose-response effects of isoflurane and halothane anesthesia on hemodynamics and coronary artery reactivity, the authors studied myocardial hyperemic responses following brief single artery flow arrests in 21 open chest, isocapnic swine in which arterial blood pressures and cardiac outputs were recorded. A specially designed Doppler probe was used to measure the peak and time course of coronary blood flow velocity in the left anterior descending coronary artery (LAD) after 15-s LAD occlusions. The ratio of peak velocity of blood flow to resting velocity (coronary reserve), relative repayment of flow debt, and duration of hyperemic responses were studied. Surgery was performed at MAC end-tidal concentrations ([Et]isoflurane = 1.45%. [Et]halothane = 1.25%) of isoflurane (n = 7) or halothane (n = 7), and recordings were made after 15-min steady state [Et]agent at 0.5, 1, 1.25, 1.5, 1.75, 2 MAC, and further 0.5 MAC increments until the demise of each animal. To compare coronary reactivity at similar coronary pressures, an aortic snare was used to elevate arterial pressures in a third group of halothane anesthesized pigs (n = 7) to those in the previously studied isoflurane group at each MAC level. There were three major differences between halothane and isoflurane. First, cardiac depression (reduction in arterial pressure, cardiac output, and stroke volume) was less with isoflurane compared with halothane anesthesia. Second, with halothane anesthesia, there was a marked decrease in coronary reactivity independent of coronary perfusion pressures with marked, dose-dependent reductions in both coronary reserve and relative flow repayment. During isoflurane anesthesia, coronary reactivity and coronary reserve was well preserved within physiologic limits up to 1.75 MAC [Et]. Third, halothane anesthesized pigs died in cardiac collapse at much lower agent concentrations than with isoflurane (no animals survived 1.75 MAC halothane, whereas all animals survived 2.5 MAC isoflurane). Therefore, pigs anesthesized with isoflurane had greater coronary reserve, better preserved cardiac function, and greater tolerance to increasing agent concentration than pigs anesthesized with halothane.     

Effects of sevoflurane and isoflurane on the ratio of cerebral blood flow/metabolic rate for oxygen in neurosurgery

Purpose. To examine the changes in cerebral blood flow (CBF) equivalent (CBF divided by cerebral metabolic rate for oxygen) during craniotomy under isoflurane and sevoflurane anesthesia in patients with intracranial disorders. Method. In 16 neurosurgical patients (8 anesthetized with isoflurane and 8 with sevoflurane), the CBF equivalent was measured while the end-tidal concentration of the selected volatile anesthetic was maintained at 0.5 and 1.0 minimum alveolar concentration (MAC) before surgery, and then 1.0 MAC during surgery, which lasted more than 4 h. Results. There was no significant difference in CBF equivalent at 0.5 MAC between the isoflurane (20 ± 4 ml blood/ml oxygen) and the sevoflurane (19 ± 4 ml blood/ml oxygen) groups. With increasing anesthetic depth from 0.5 to 1.0 MAC, the CBF equivalent significantly (P < 0.05) increased in both groups (22 ± 7 and 21 ± 5, respectively). At 1.0 MAC during operation, the CBF equivalent with both anesthetics was maintained with minimal fluctuation for 4 h. There were no significant differences in the average value of the CBF equivalent during a 4-h period at 1.0 MAC between the isoflurane (23 ± 5) and the sevoflurane (20 ± 4) groups. Conclusion. Deepening anesthesia from 0.5 to 1.0 MAC with isoflurane and sevoflurane produced a slight increase in the CBF equivalent. The CBF equivalent at 1.0 MAC was maintained with no difference between the two agents during 4 h of neurosurgery. Received: August 2, 1999 / Accepted: April 3, 2000     

Isoflurane and sevoflurane decrease entropy indices more than halothane at equal MAC values

Recently, bispectral index (BIS) values were demonstrated to be different for various anesthetics as a result of differential effects on electroencephalographic (EEG) signals. Entropy is similar to the BIS monitor, as both process raw EEG to derive a number. We hypothesized that entropy may also be anesthetic agent-specific. Thirty adult patients undergoing spinal surgery were randomized to receive halothane, isoflurane, or sevoflurane. Entropy indices were recorded at various minimum alveolar concentration (MAC) values—0.5, 0.75, 1.0 and 1.5—both during wash-in and wash-out of the agent. Heart rate (HR), mean arterial blood pressure (MAP), response entropy (RE), and state entropy (SE) were noted. Statistical analysis was done using a one-way analysis-ofvariance test. P values less than 0.05 were considered significant. Ten patients in each group completed the study. The demographics and baseline values of HR, MAP, RE, and SE were comparable in all three groups. During the study period, for a given MAC value, both RE and SE remained low in the isoflurane and sevoflurane groups compared to the halothane group. For a given MAC, the RE and SE were comparable during wash-in and wash-out phases. Halothane produced higher entropy values as compared to isoflurane and sevoflurane at equivalent MAC levels.     

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)     

Gastric Mucosal Perfusion in Dogs: Effects of Halogenated Anesthetics and of Hemorrhage

The gastrointestinal tract is one of the first organs affected by hypoperfusion during hemorrhagic shock. The hemodynamics and oxygen transport variables during hemorrhagic shock and resuscitation can be affected by the anesthetics used. In a model of pressure-guided hemorrhagic shock in dogs, we studied the effects of three halogenated anesthetics—halothane, sevoflurane, and isoflurane—at equipotent concentrations on gastric oxygenation. Thirty dogs were anesthetized with 1.0 minimum alveolar anesthetic concentration (MAC) of either halothane, sevoflurane, or isoflurane. A gastric tonometer was placed in the stomach to determine mucosal gastric CO₂ (PgCO₂) and for the calculation of gastric-arterial PCO₂ gradient (PCO₂ gap). The dogs were splenectomized and hemorrhaged to hold mean arterial pressure at 40–50 mm Hg over 45 min and then resuscitated with the shed blood volume. Hemodynamics, systemic oxygenation, and PCO₂ gap were measured at baseline, after 45 min of hemorrhage, and at 15 and 60 min after blood resuscitation. Hemorrhage induced reductions of mean arterial pressure and cardiac index, while systemic oxygen extraction increased (p <. 05), without significant differences among groups (p >. 05). Halothane group showed significant lower PCO₂ gap values than the other groups (p <. 05). After 60 min of shed blood replacement, all groups restored hemodynamics, systemic oxygenation, and PCO₂ gap to the prehemorrhage levels (p >. 05), without significant differences among groups (p >. 05). We conclude that halothane is superior to preserve the gastric mucosal perfusion in comparison to isoflurane and sevoflurane, in dogs submitted to pressure-guided hemorrhagic shock at equipotent doses of halogenated anesthetics.     

CEREBRAL EFFECTS OF SEVOFLURANE IN THE DOG: COMPARISON WITH ISOFLURANE AND ENFLURANE

The cerebral effects of sevoflurane were compared in dogs withthose of enflurane and isoflurane. Initially, the minimum alveolarconcentrations (MAC) of sevoflurane and enflurane were determinedand the electroencephalo-graphic (EEG) responses to increasingdoses of sevoflurane (1.5, 2.0 and 2.5 MAC) or enflurane (1.5and 2.0 MAC) in unparalysed animals were examined. Administrationof sevoflurane was not associated with seizure activity at anyconcentration either during normocapnia (Pa_CO2 5.3 kPa) or hypocapnia(Pa_CO2 2.7 kPa), even in the presence of intense auditory stimuli.All dogs anaesthetized with enflurane demonstrated sustainedEEG and motor evidence of seizure activity induced by auditorystimuli at concentrations of enflurane > 1 MAC, particularlyduring hypocapnia. In a separate group of dogs, the effectsof increasing concentrations of sevoflurane and isoflurane (0.5,1.5 and 2.15 MAC) were compared directly on arterial pressure,cardiac output and heart rate, cerebral blood flow and the cerebralmetabolic rate for oxygen (CMRO₂) using the venous outflow technique.Sevoflurane, in common with isoflurane, had minimal effectson cerebral blood flow at the concentrations studied, but significantlyreduced the CMRO₂ at end-tidal concentrations sufficient toproduce a burst suppression pattern on the EEG (approximately2.15 MAC). Both sevoflurane and isoflurane significantly decreasedarterial pressure in a dose-dependent manner, but neither drugsignificantly altered cardiac output.     

Direct vasodilation by sevoflurane, isoflurane, and halothane alters coronary flow reserve in the isolated rat heart

Direct vasodilation of coronary resistance vessels by anesthetics may reduce coronary flow reserve and interfere with myocardial flow-metabolism coupling. This study was performed to evaluate the potential for the halogenated anesthetic agents sevoflurane, isoflurane, and halothane to alter the regulation of coronary flow via a direct action on coronary resistance vessels. Coronary flow and flow reserve were measured in the quiescent isolated perfused rat heart at anesthetic concentrations between 0 and 3 x MAC. In order to minimize anesthetic-induced secondary changes in coronary resistance, constant coronary perfusion pressure was maintained; the left ventricular cavity was vented; and tetrodotoxin was used to achieve cardiac arrest. These conditions permitted the dissociation of direct anesthetic actions from indirect regulatory processes affecting coronary vascular resistance (CVR). Coronary flow reserve was defined as the difference between coronary flow prior to and during administration of a maximally vasodilating dose of adenosine. Each anesthetic significantly reduced the magnitude of both CVR and coronary flow reserve in a concentration-dependent manner. Sevoflurane reduced coronary flow reserve significantly less than did halothane and isoflurane. At high concentrations (3.0 x MAC), coronary flow reserve was abolished by halothane and was decreased to near zero by isoflurane; however, flow reserve was reduced only 48% from control by sevoflurane. This difference among anesthetics is explained primarily by variations in the magnitude of direct coronary vasodilation produced by each anesthetic, rather than by effects on maximal vasodilator capacity. These data show that sevoflurane's intrinsic vasodilator action on coronary resistance vessels differs substantially from that of halothane and isoflurane.     

Intrabiliary pressure changes produced by inhalational anesthetics in dogs]

The common bile duct pressure was studied in dogs under inhalation of 1.0 MAC and 2.0 MAC of halothane, enflurane, isoflurane or sevoflurane. A double lumen catheter was inserted into the common bile duct through the cholecystic duct for the measurement of intraductal pressure in the choledochoduodenal junction. The intra-bile-ductal pressure (IBP) was measured with constant rate infusion methods every 10 minutes for one hour. After obtaining control IBP measurements, 44 dogs received randomly either 1.0 MAC (n = 6 in each group) or 2.0 MAC (n = 5 in each group) of each four inhalational anesthetics, through a non-rebreathing system. The decreases in IBP produced by 1.0 MAC concentrations of four inhalation anesthetics were not statistically significant although there was a decline from control measurements obtained for each group. The elevations of IBP following 2.0 MAC halothane, isoflurane or sevoflurane were significantly depressed and were 38.3 +/- 21.2, 67.5 +/- 23.8, 63.7 +/- 23.7 (%, mean +/- SD) of the control levels, respectively. However, 2.0 MAC enflurane produced no significant decrease in IBP.     

Comparison of the effects of sevoflurane and isoflurane anesthesia on the maternal-fetal unit in sheep

Purpose  The aim of this study was to determine the hemodynamic and blood gas effects of inhalational anesthetics on the maternal-fetal sheep unit. The principal hypothesis, tested in chronically instrumented near-term pregnant ewes, was that sevoflurane anesthesia may be safe and useful for the mother and fetus during pregnancy, compared with isoflurane. Methods  Six chronically instrumented pregnant and 3 nonpregnant ewes were tested repeatedly to establish the minimum alveolar concentration (MAC) for sevoflurane and isoflurane to be used in the hemodynamic and blood gas studies. Progressively increasing concentrations of sevoflurane or isoflurane in oxygen were administered to 12 pregnant ewes. Uterine blood flow, maternal and fetal heart rates, blood pressure, arterial blood gases, and intra-amniotic pressure were subsequently measured. Results  The MAC of sevoflurane was 1.52 ± 0.1 15% and 1.92 ± 0.17% in pregnant and nonpregnant ewes, respectively; while the MAC of isoflurane in the pregnant and nonpregnant sheep was 1.02 ± 0.12% and 1.42 ± 0.19%, respectively. In both the sevoflurane and isoflurane groups, changes in maternal and fetal blood gases were minimal during exposure to low-dose (0.5–1.0 MAC) inhaled concentrations. Although uterine blood flow was maintained and the fetus remained well oxygenated at higher concentrations of both agents (2.0 MAC of either agent), the agents produced decreases in maternal and fetal arterial pressure. Conclusion  A “low-dose” concentration (0.5–1.0 MAC) of sevoflurane may be safe and useful for both mother and fetus during near-term pregnancy. However, a high concentration (1.5–2.0 MAC) of sevoflurane or isoflurane may induce hemodynamic instability in the mother and fetus when administered.     

Direct coronary vasomotor effects of sevoflurane and desflurane in in situ canine hearts

BACKGROUND: An extracorporeal system was used to investigate the direct coronary vasomotor effects of sevoflurane and desflurane in vivo. The role of the adenosine triphosphate-sensitive potassium channels (KATP channels) in these effects was evaluated. METHODS: Twenty-one open-chest, anesthetized (fentanyl-midazolam) dogs were studied. The left anterior descending coronary artery was perfused at controlled pressure (80 mmHg) with normal arterial blood or arterial blood equilibrated with either sevoflurane or desflurane. Series 1 (n = 16) was divided into two groups of equal size on the basis of whether sevoflurane (1.2, 2.4, and 4.8%) or desflurane (3.6, 7.2, and 14.4%) was studied. The concentrations for the anesthetics corresponded to 0.5, 1.0, and 2.0 minimum alveolar concentration (MAC), respectively. Coronary blood flow (CBF) was measured with an ultrasonic, transit-time transducer. Local coronary venous samples were obtained and used to evaluate changes in myocardial oxygen extraction (EO2). In series 2 (n = 5), changes in CBF by 1 MAC sevoflurane and desflurane were assessed before and during intracoronary infusion of the KATP channel inhibitor glibenclamide (100 microg/min). RESULTS: Intracoronary sevoflurane and desflurane caused concentration-dependent increases in CBF (and decreases in EO2) that were comparable. Glibenclamide blunted significantly the anesthetic-induced increases in CBF. CONCLUSIONS: Sevoflurane and desflurane have comparable coronary vasodilative effects in in situ canine hearts. The KATP channels play a prominent role in these effects. When compared with data obtained previously in the same model, the coronary vasodilative effects of sevoflurane and desflurane are similar to those of enflurane and halothane but considerably smaller than that of isoflurane.     

Anticonvulsant effects of sevoflurane on amygdaloid kindling and bicuculline-induced seizures in cats: comparison with isoflurane and halothane

Purpose. We compared the anticonvulsant effects of sevoflurane with those of isoflurane and halothane in amygdaloid kindling and bicuculline-induced seizures in cats. Methods. In a crossover design, the effects of 70% nitrous oxide, and 0.3, 0.6, and 1.5 minimum alveolar concentration (MAC) of volatile anesthetics were studied in five cats in which the amygdala was electrically stimulated at the current used for establishing the kindled state. The effects of 0.6 and 1.5 MAC of volatile anesthetics were studied in another five cats, in which 0.2 mg·kg⁻¹ of bicuculline was administered IV. Results. In the amygdaloid kindling model, all four anesthetics decreased the duration of after-discharge (AD), the rise of multiunit activity in midbrain reticular formation (R-MUA), and the behavior scores compared with findings without anesthetics. Halothane, at 1.5 MAC, significantly decreased the number of cats showing AD (P < 0.05). In the bicuculline-induced seizure model, all five cats showed repetitive spikes during 1.5 MAC of sevoflurane, whereas only two and three cats, respectively, showed the repetitive spikes during 1.5 MAC of isoflurane and halothane. All three volatile anesthetics decreased the rise of R-MUA, the duration of the repetitive spikes, and the behavior scores. The suppression of the rise in R-MUA and the behavior scores with 1.5 MAC of sevoflurane was significantly less than that with 1.5 MAC of isoflurane. Conclusion. The anticonvulsant effects of sevoflurane were less potent than those of halothane in the amygdaloid kindling model and less potent than those of isoflurane in the bicuculline-induced seizure model. Received: January 11, 2001 / Accepted: May 9, 2001     

Effects of halothane, enflurane, and isoflurane on coronary blood flow autoregulation and coronary vascular reserve in the canine heart

To investigate the effects of volatile anesthetics on coronary blood flow (CBF) autoregulation and coronary vascular reserve, studies were performed on chronically instrumented dogs, awake and during the administration of 1.0 MAC halothane, enflurane, and isoflurane. Coronary pressure-flow plots were generated by measuring left anterior descending coronary artery blood flow while varying coronary inflow pressure with a hydraulic occluder. Autoregulation was quantitated by two measures: the slope of the horizontal "autoregulated" portion of the pressure-flow relationship and the autoregulation index (ArI) of Norris. Slope values (ml.min-1.mmHg-1 +/- SD) were: awake, 0.243 +/- 0.043; halothane, 0.414 +/- 0.044; enflurane, 0.587 +/- 0.187; and isoflurane, 0.795 +/- 0.246. The increase in slope was statistically significant only for halothane and isoflurane (P less than .05). The ArI approaches 1.0 when autoregulation is perfect, and approaches zero or is a negative number when autoregulation is absent. The authors found ArI values of: awake, 0.55; halothane, -0.08; enflurane, -0.01; isoflurane, -0.02. These values indicate good autoregulation while awake, but impaired autoregulation with all three anesthetics (P less than .05). Coronary vascular reserve was calculated, at a diastolic coronary pressure of 40 mmHg, as the difference between resting flow and flow during maximal coronary vasodilation induced by intracoronary adenosine. Coronary vascular reserve, maximal coronary conductance, and coronary zero-flow pressure were not significantly altered by these anesthetics. The authors conclude that 1.0 MAC enflurane, halothane, and isoflurane mildly disrupt CBF autoregulation, increasing CBF out of proportion to myocardial demands. Under the conditions of this study, these anesthetics do not affect maximal CBF or coronary vascular reserve.     

Effect of halothane, isoflurane and desflurane on lower oesophageal sphincter tone

We have studied the effects of volatile anaesthetics on lower oesophageal sphincter (LOS) tone in three groups of eight pigs allocated randomly to receive end-tidal concentrations of 0.5, 1.0 and 1.5 MAC of desflurane, isoflurane or halothane for 15 min. LOS and oesophageal barrier pressures (BrP = LOSP - gastric pressure) were measured using a manometric method. The decrease in BrP paralleled the decrease in LOS pressure and was significant at 0.5 MAC for isoflurane and at 1.0 MAC for halothane. At 1.5 MAC, BrP values were approximately 62% of baseline values for halothane, 37% for isoflurane and 83% for desflurane. Inter-group comparisons showed that BrP did not differ at baseline and at 0.5 MAC. At 1.0 MAC the effect of isoflurane on BrP was significantly different from desflurane (P < 0.001) and halothane (P < 0.02) whereas the effect of desflurane on BrP was not significantly different from halothane. At 1.5 MAC the effect of isoflurane on BrP was significantly different from desflurane (P < 0.01) and halothane (P < 0.05) whereas the effect of desflurane on BrP was not significantly different from halothane. We conclude that desflurane maintained BrP and this may be clinically important in patients at high risk of regurgitation.      

Neutrophils pretreated with volatile anesthetics lose ability to cause cardiac dysfunction

BACKGROUND: Volatile anesthetics can precondition the myocardium against functional depression and infarction following ischemia-reperfusion. Neutrophil activation, adherence, and release of superoxide play major roles in reperfusion injury. The authors tested the hypothesis that pretreatment of neutrophils with a volatile anesthetic, i.e., simulated preconditioning, can blunt their ability to cause cardiac dysfunction. METHODS: Studies were performed in 60 buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as an index of myocardial contractility. Polymorphonuclear neutrophils and/or drugs were added to coronary perfusate for 10 min, followed by 30 min of recovery. Platelet-activating factor was used to stimulate neutrophils. Pretreatment of neutrophils consisted of incubation with 1.0 minimum alveolar concentration (MAC) isoflurane or sevoflurane for 15 min, followed by washout. Additional studies were performed with 0.25 MAC isoflurane. Effects of superoxide dismutase were compared to those of volatile anesthetics. Superoxide production was measured by spectrophotometry. Neutrophil adherence to coronary vascular endothelium was estimated from the difference between neutrophils administered and recovered in coronary venous effluent. RESULTS: Activated neutrophils caused marked, persistent reduction (> 50%) in left ventricular developed pressure. Isoflurane and sevoflurane at 1.0 MAC and superoxide dismutase abolished this effect. Isoflurane and sevoflurane reduced superoxide production of activated neutrophils by 29% and 33%, respectively, and completely prevented the platelet-activating factor-induced increases in neutrophil adherence. Isoflurane at 0.25 MAC blunted, but did not abolish, the neutrophil-induced decreases in left ventricular developed pressure. CONCLUSION: Neutrophils pretreated with 1.0 MAC isoflurane or sevoflurane lost their ability to cause cardiac dysfunction, while those pretreated with a concentration of isoflurane as low as 0.25 MAC were partially inhibited. This action of the volatile anesthetics was associated with reductions in superoxide production and neutrophil adherence to the coronary vascular endothelium. Our findings suggest that inhibitory actions on neutrophil activation and neutrophil-endothelium interaction may contribute to the preconditioning effects of volatile anesthetics observed in vivo during myocardial ischemia-reperfusion.     

Comparison of the effects of sevoflurane, isoflurane and halothane on rat myocardium

The effects of sevoflurane on myocardial contraction and relaxation are poorly understood. Therefore, we studied the effects of equianaesthetic concentrations (0.5, 1, 1.5, 2 and 2.5 MAC) of sevoflurane, isoflurane and halothane on inotropic and lusitropic (myocardial relaxation) variables, and post-rest potentiation in rat left ventricular papillary muscles in vitro. Sevoflurane and isoflurane caused comparable concentration-dependent negative inotropic effects which were significantly lower than those induced by halothane (P < 0.05). Sevoflurane and isoflurane did not modify lusitropic variables under low or high load, whereas halothane showed a negative lusitropic effect at high concentrations. Halothane suppressed post-rest potentiation, whereas isoflurane and sevoflurane did not. Post-rest recovery was unaffected by halothane, isoflurane or sevoflurane at any concentration. Thus in rat myocardium, sevoflurane and isoflurane caused comparable negative inotropic effects, had no significant lusitropic effects and did not alter post-rest potentiation, suggesting that they did not significantly modify the functions of the sarcoplasmic reticulum.      

Hemodynamic responses to nitrous oxide during inhalation anesthesia in pediatric patients

STUDY OBJECTIVE: To measure the hemodynamic changes produced by nitrous oxide (N2O) during halothane and isoflurane anesthesia in infants and children. DESIGN: A repeated measures design in two groups of infants and small children. SETTING: Operating rooms at a university hospital. PATIENTS: Nineteen healthy unmedicated infants and small children (mean age 12 months) who required elective surgery. INTERVENTIONS: Prior to anesthesia induction, cardiovascular measurements were recorded using pulsed Doppler and two-dimensional echocardiography. Following anesthesia induction with halothane (n = 10) or isoflurane (n = 9) in oxygen (O2) and air, anesthetic measures were stabilized at 1.0 minimum alveolar concentration (MAC) and cardiovascular measures were repeated. After 30% N2O was added to the 1.0 MAC anesthetic concentration, a third set of cardiovascular measurements was recorded. A final cardiovascular data set was measured 5 minutes following an increase in N2O concentration to 60%. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (MAP), cardiac index (CI), stroke volume (SV), and ejection fraction (EF) decreased similarly and significantly at 1.0 MAC halothane and isoflurane. Heart rate (HR) increased during isoflurane anesthesia but decreased during halothane anesthesia. The addition of N2O resulted in a decrease in HR, CI, and MAP when compared to 1.0 MAC levels of halothane or isoflurane; however, SV and EF were not significantly changed from levels measured during 1.0 MAC halothane or isoflurane. CONCLUSIONS: The addition of N2O to halothane and isoflurane anesthesia in infants and children decreased HR. This decrease led to a decrease in cardiac output (CO). Unlike with adults, N2O did not produce cardiovascular signs of sympathetic stimulation in infants and children.