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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a ceiling to the reduction of enflurane MAC by fentanyl in the dog. Sufentanil (SUF), a more potent narcotic, may be more efficacious in reducing enflurane MAC. To test this hypothesis, 25 mongrel dogs were studied in three groups. Group 1 (n = 8) received SUF in progressively increasing infusion rates from 0.005 micrograms . kg-1 . min-1 to a maximum of 1.215 micrograms . kg-1 . min-1. MAC was determined at stable SUF concentrations in plasma [SUF] during each infusion rate. Group 2 (n = 10) received SUF at a dose rate (0.007 micrograms . kg-1 . min-1) designed to produce approximately 35% MAC reduction, and MAC determinations were made at regular intervals over a mean infusion time of 7.6 +/- 0.43 h (mean +/- SEM). Group 3 (n = 7) received 1.215 micrograms . kg-1 . min-1 and were studied as in group 2 over an infusion time of 6.7 +/- 0.42 h. In group 1, the highest infusion rate (1.215 micrograms . kg-1 . min-1) produced [SUF] = 48 ng/ml and reduced MAC by 71 +/- 6%. This was not statistically different from the reduction which occurred at [SUF] = 0.92 ng/ml (57 +/- 7%; infusion rate 0.015 micrograms . kg-1 . min-1; P = 0.21). In group 2, the degree of MAC reduction achieved by stable [SUF] (0.54 +/- 0.08 ng/ml) declined over time (MAC reduction at start = 34 +/- 2% versus 18 +/- 4.0% at the end of the infusion; P = 0.001), suggesting the development of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The enflurane sparing effect of sufentanil in dogs. 295 71

We studied the effect of halothane, enflurane and isoflurane on angiotensin converting enzyme (ACE) activity using [3H]-benzoyl-phenylalanyl-alanyl-proline (BPAP) as a substrate. Isolated rabbit lungs were perfused in a recirculating system in vitro with BPAP in Krebs-Ringer solution. The rate of metabolism and per cent metabolism were determined before and after treatment for 30 minutes with four MAC multiples of enflurane, halothane or isoflurane. The effects of the anaesthetics on ACE activity were determined by calculating per cent inhibition of metabolism of BPAP using data from the control and test period for each lung. The average metabolism of BPAP at 15 minutes during the control period was 76.5 per cent (+/- 1.92 SEM). No anaesthetic significantly inhibited metabolism of BPAP. Likewise there was no effect on BPAP first order kinetics. Although potent inhalation anaesthetics may alter the renin-angiotensin-aldosterone axis, they do not affect this crucial step.
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PMID:Enflurane, halothane and isoflurane do not inhibit angiotensin converting enzyme activity. 299 30

A critical level of oxygen transport has been defined as the level which is required to maintain tissue oxygen uptake (VO2). If halothane reduces the susceptibility to hypoxia, it should lower the critical levels of both O2 delivery (DO2) and arterial oxygen tension (pO2). To test this hypothesis, 12 newborn lambs were anesthetized with either fentanyl and pancuronium (control group) or fentanyl, pancuronium, and 1.1% (1 MAC) halothane (halothane group). Baseline measurements of hemoglobin, cardiac output (CO), arterial and mixed-venous pO2, and saturation were obtained on FIO2 1.0, and repeated with FIO2 .21, .15, and .10. O2 delivery (CO X CaO2) and O2 consumption were calculated from measured parameters. Critical levels were selected using a system of repetitive linear regression. Halothane decreased baseline O2 consumption (12.1 +/- 0.7 to 8.4 +/- 0.4 cc X kg-1 X min-1, x +/- SEM, P less than .001, unpaired t test), but caused similar reductions in cardiac output (235 +/- 15 to 132 +/- 15 cc X kg-1 X min-1, P less than .001) and O2 delivery (29.2 +/- 2.9 to 20.2 +/- 1.6 cc X kg-1 X min-1, P less than .05). Addition of halothane decreased the critical level of O2 delivery from 17.9 to 14.3 cc X kg-1 X min-1, but had no effect on the critical level of arterial pO2 (control group, 47 mmHg halothane, 46 mmHg). Peripheral oxygen utilization was mildly reduced during halothane anesthesia, as evidenced by a decrease in oxygen extraction (control group O2 extraction rate = 0.63; halothane group O2 extraction = 0.51, P less than .05, unpaired t test).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of halothane on critical levels of oxygen transport in the anesthetized newborn lamb. 311 9

Regional (frontal, parietal, occipital, cortical, and basal ganglia) cerebral blood flow (rCBF) was examined at 1.5 and 3.5 MAC inspired isoflurane/O2 anesthesia in the rat using the radioactive microsphere technique to determine the effects of controlled hypotension with deep isoflurane anesthesia on rCBF and the response of rCBF to changes in PaCO2 when mean blood pressure (BP) was decreased to levels below the lower limit of the autoregulatory threshold. Four groups of six rats were studied with rCBF 1 determined at 1.5 MAC (mean BP 80-90 mm Hg) followed by two rCBF determinations at 3.5 MAC (mean BP 46-48 mm Hg). For CBF 1 the regional CO2 response was a 3.1-3.9% increase in rCBF/mm Hg increase in CO2. Regional cerebral blood flow (ml/g/min) ranged from 0.64 +/- 0.05-0.83 +/- 0.15 at PaCO2 of 19 mm Hg to 1.34 +/- 0.11-1.80 +/- 0.33 at PaCO2 of 41 mm Hg to 2.61 +/- 0.26-3.72 +/- 0.37 at PaCO2 of 59 mm Hg (mean +/- SEM). With controlled hypotension (CBF 2) rCBF was unchanged during normocarbia, increased 100% during hypocarbia, P less than 0.01 vs CBF 1 and decreased 30% during hypercarbia, P less than 0.01 vs CBF 1. For rCBF 3 measurements, the BP and inspired concentration of isoflurane were kept constant, while PaCO2 was increased in two and decreased in two of the four groups. Within-group comparisons between rCBF 2 and rCBF 3 results demonstrated loss of CO2 responsiveness of the rat cerebrovasculature in every region during controlled hypotension to below the autoregulatory threshold at 3.5 MAC isoflurane/O2 anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional cerebral blood flow and response to carbon dioxide during controlled hypotension with isoflurane anesthesia in the rat. 312 43

Midazolam (Mid) is widely used as an anesthetic adjunct. To test its anesthetic effect vs. concentration relationships, it is desirable to establish stable and predictable Mid concentrations in plasma (and brain). Therefore, the pharmacokinetics of Mid in the enflurane-anesthetized dog were determined, and the ability of Mid to reduce the enflurane concentration required for anesthesia was measured and correlated with the Mid concentration in plasma [MID]. Mongrel dogs (n = 9) were anesthetized with enflurane and the enflurane EC50 (MAC--the end-tidal concentration at which one-half of the dogs respond to the noxious stimulation of clamping of the tail, and one-half do not) was determined. Group 1 (n = 5) received Mid 2.5 mg/kg iv over 60 sec. Plasma for determination of [MID] was collected and the enflurane EC50 was determined repeatedly over the 7-8-hr period following injection. Based on the pharmacokinetic parameters determined for Group 1, dogs in Group 2 (n = 4) received Mid as a continuous infusion of 21 micrograms kg-1 min-1 for 5 hr accompanied by an initial loading dose (3 mg/kg infused over 20 min) designed to produce a stable [MID] of 1000 ng/ml in plasma. Enflurane MAC and [MID] were determined regularly during the infusion and for 6 hr after discontinuation of the infusion. There were no important differences in the pharmacokinetic parameters determined for Group 1 vs. Group 2: t1/2,z = 98 +/- 5 vs. 95 +/- 10 min (mean +/- SEM); V = 3.94 +/- 0.27 vs. 2.98 +/- 25 L/kg; Cl = 28.5 +/- 3.1 vs. 22.3 +/- 1.1 ml kg-1 min-1, respectively. When administered as a continuous intravenous infusion (Group 2), [MID] remained stable at 949 +/- 53 ng/ml for more than 5 hr. The enflurane EC50 was reduced by 55% and the reduction remained stable during the 5 hours of Mid infusion. After a single iv bolus dose or after discontinuation of the continuous infusion, the degree of enflurane EC50 reduction diminished toward the control (i.e., enflurane alone) value as [MID] declined. Mid-azolam's pharmacokinetics and plasma concentration vs. effect relationships have been determined to be consistent under two different experimental conditions.
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PMID:Pharmacokinetics and pharmacodynamics of midazolam in the enflurane-anesthetized dog. 322 25

This study determined the anesthetic efficacy of midazolam (MID) in terms of its ability to reduce enflurane MAC (EMAC). Control EMAC was determined by the tail-clamp method in 15 mongrel dogs. Each animal then received at least three incremental infusion rates of MID from among the following: 0.48, 2.4, 9.6, 19.2, 28.8, 48, or 151.2 micrograms.kg-1.min-1. MAC was determined during each infusion rate following a 1-h observation period, during which time MID concentration in plasma [( MID]) stabilized. [MID] was measured every 15 min beginning 45 min from the start of each new infusion rate. There was a linear relationship between MID infusion rates and the resulting [MID] (r = 0.995). In the range of [MID] from 14 to 14,118 ng/ml, there was a linear relationship between the log [MID] and the percent EMAC reduction. The slope of the line was very shallow, and the [MID] required to reduce EMAC by more than 50% exceeded the [MID] likely to be employed clinically in humans (750 ng/ml). Also, the 73 +/- 4% (mean +/- SEM) EMAC reduction produced by [MID] = 9,763 +/- 1213 ng/ml was not significantly greater than the 60 +/- 3% EMAC reduction achieved by [MID] = 1,464 +/- 293 ng/ml, a finding which suggests a ceiling effect to the anesthetic efficacy of midazolam. The authors conclude that, within the dose range of MID likely to be employed in humans, MID produced a concentration-dependent reduction of enflurane MAC in the dog. In doses above those likely to be employed clinically, a ceiling effect to the anesthetic efficacy of MID may become evident.
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PMID:The anesthetic efficacy of midazolam in the enflurane-anesthetized dog. 337 32

Nocturnal sleep was studied in eight healthy young volunteers before and after isoflurane anesthesia. All night polysomnographic recordings were obtained for seven consecutive nights from approximately 2300 to 0700 h. On the morning after the third night each subject was anesthetized with isoflurane 1.1 MAC for approximately 3 h. The stages and indices of nocturnal sleep were calculated for each night of study according to standard criteria. The effects of anesthesia on nocturnal sleep were confined to the first postanesthetic night. Slow wave sleep (Stages 3 and 4) was moderately suppressed from 16 +/- 1% to 6 +/- 1%, and Stage 2 sleep reciprocally increased from 52 +/- 2% to 60 +/- 2% (mean +/- SEM, P less than 0.05). There were no detectable changes in the sleep onset latency, the total quantity of sleep, or the proportion of rapid eye movement (REM) sleep. Anesthesia was followed by daytime napping in six of the eight volunteers. Nocturnal sleep was similar in the subjects who napped and those who did not. It is concluded that anesthesia with isoflurane leads to a modest and a transient change in the architecture of nocturnal sleep.
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PMID:Isoflurane anesthesia causes a transient alteration in nocturnal sleep. 341 13

The fatal/anesthetic ratio (FAR) in 44 swine weighing 32.6 +/- 0.7 kg (SEM) was determined. Fatal anesthetic concentration (the numerator for FAR) was defined as the end-tidal concentration at which the pig lived at least 10 min, during experiments that involved step increments in anesthetic concentrations. Previously reported MAC was used as the "anesthetic" concentration (denominator) to determine FAR. Halothane was compared to isoflurane and the question of whether major surgery might reduce FAR was investigated. The major surgery groups included one open chest group with each volatile anesthetic studied during coronary reserve measurements, and two groups that had LAD critical coronary stenoses. Thus volatile agents were compared with vs without major surgery, and with vs without a critical coronary stenosis. The FAR for isoflurane was approximately double that of halothane. Further, addition of major surgery did not produce significant deterioration in FAR with isoflurane. In contrast, with halothane there was a significant (approximately 20%) decrease in FAR, despite values already only half that seen with isoflurane, when major surgery was added. Presence of a critical coronary stenosis was not associated with a worsened FAR for isoflurane or halothane. It was concluded that the fatal/anesthetic ratio for isoflurane in pigs is 1.9 times greater than that for halothane. Addition of major surgery did not affect FAR when isoflurane was the anesthetic but did when halothane was used. Critical coronary stenosis did not worsen FAR. Because these results are nearly identical with those reported previously in small mammals, the doubled safety margin seen with isoflurane may have clinical relevance.
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PMID:Isoflurane has a greater margin of safety than halothane in swine with and without major surgery or critical coronary stenosis. 357 60

The objective of this investigation was to compare the effects of the commonly used volatile anesthetics on concentrations of plasma and cerebral glucose and cerebral intermediary metabolites. Fasted male Long-Evans rats were anesthetized with a volatile anesthetic and, after tracheostomy and paralysis, were mechanically ventilated. Each of three groups received one MAC concentration of anesthesia with halothane, enflurane, or isoflurane. At the end of 60-75 min of anesthesia, blood was sampled for arterial blood gas and plasma glucose analysis, and the brain was rapidly sampled and frozen for analysis of energy metabolites. Physiologic variables were maintained as follows: PaCO2 30-40 mmHg, pHa 7.20-7.40, PaO2 greater than 60 mmHg, MAP greater than 60 mmHg, and rectal temperature 37.5-38.5 degrees C. Mean plasma glucose concentrations in the three groups were as follows (muMol/ml +/- SEM): halothane, 7.45 /- .62; enflurane, 6.95 +/- .22; isoflurane, 10.11 +/- 1.00. Mean brain glucose concentrations in the three groups were (muMol/gm wet weight): halothane, 2.04 +/- .20; enflurane, 2.07 +/- .26; isoflurane, 3.04 +/- .31. Plasma and brain glucose levels were significantly increased in the isoflurane group compared to the other two groups (P less than .05) with no differences occurring in the brain/plasma glucose ratio among the three groups. No differences were present between groups in brain lactate, pyruvate, fructose diphosphate, malate, alpha-ketoglutarate, phosphocreatine, or adenine nucleotides. Thus, at one MAC concentration, major differences between volatile anesthetics on brain energy availability are not present, although isoflurane raised cerebral glucose levels.
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PMID:Comparison of the effects of volatile anesthetics on brain glucose metabolism in rats. 359 79

The combination of two-dimensional and pulsed Doppler echocardiography was used to measure determinants of cardiac function in 20 ASA physical status I infants and small children (9 days-32 months of age) during equipotent halothane (n = 10) or isoflurane (n = 10) anesthesia in oxygen. Five sets of cardiovascular data were recorded in each patient. In the awake, unmedicated state prior to induction, at three different anesthetic levels, 0.75, 1.0, and 1.25 MAC (corrected for age) and a final measurement repeated at 1.25 MAC after the intravenous infusion of 15 ml X kg-1 of Lactated Ringers solution. The study was completed prior to intubation and surgery. Results are expressed as mean +/- SEM. Isoflurane and halothane decreased mean blood pressure from the awake level (isoflurane 76.6 +/- 2.3 to 60.6 +/- 3.1 mm, halothane 72.2 +/- 3.9 to 60.6 +/- 3.1 mm at 1.25 MAC). Isoflurane increased heart rate at all anesthetic levels (128.7 +/- 4.2 to 142.5 +/- 6.0 beats/min at 0.75 MAC). Halothane decreased heart rate at 1.25 MAC (124.6 +/- 4.6 to 119.4 +/- 3.5 beats/min). Isoflurane and halothane decreased cardiac index at 1.25 MAC. Stroke volume index decreased at 1.0 and 1.25 MAC with both isoflurane (36.9 +/- 3.8 to 30.2 +/- 3.5 ml/m2) and halothane (32.7 +/- 2.5 to 28.9 +/- 2.5 ml/m2). Ejection fractions also decreased significantly at 1.0 and 1.25 MAC in both groups of patients (22 +/- 6% at 1.25 MAC halothane and 28 +/- 8% at 1.25 MAC isoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulsed Doppler and two-dimensional echocardiography: comparison of halothane and isoflurane on cardiac function in infants and small children. 360 47


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