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11. |
The Prospective Use of Population Pharmacokinetics in a Computer‐Driven Infusion System for Alfentanil |
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Anesthesiology,
Volume 73,
Issue 1,
1990,
Page 66-72
Daniel Raemer,
Alan Buschman,
John Varvel,
Beverly Philip,
Mark Johnson,
Daniel Stein,
Steven Shafer,
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摘要:
Maitreet al.recently evaluated the accuracy of a set of previously determined population pharmacokinetic parameters for the opioid alfentanil using data from an earlier study in which the drug had been administered using a computer-controlled infusion pump (CCIP). The present study evaluated the accuracy of these same parameters in a CCIP prospectively in two groups of clinically dissimilar patients: 29 healthy female day surgery patients and 11 relatively older and less healthy male inpatients. In addition, another set of pharmacokinetic parameters, previously determined by Scottet al.in the CCIP in 11 male inpatients was also evaluated. The bias and inaccuracy were assessed by the median performance error (MDPE) and the median absolute performance error (MDAPE) in which the performance error was determined as the difference between measured and target serum concentration as a fraction of the target serum concentration. Unlike Maitreet al., the current study found a consistent bias in both populations. The MDPE was +53% and the MDAPE was 53%, with no difference between patient groups. In the 11 patients studied using the Scottet al.pharmacokinetic parameters, the MDPE was +1% and the MDAPE was 17%. The parameters of Scottet al.were further tested by simulating the serum concentrations that would have been achieved had they been used in the CCIP in the first 40 patients; results indicated MDPE of +2% and an MDAPE of 18%. Therefore, reasonably reliable and accurate target serum concentrations of alfentanil can be achieved using the pharmacokinetic parameters of Scottet al.in a CCIP. Furthermore, these pharmacokinetic parameters are more suitable for use in a CCIP than are the population pharmacokinetic parameters of Maitreet al.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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12. |
Effects of Volatile Anesthetics on Mechanical Properties of Rat Cardiac Skinned Fibers |
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Anesthesiology,
Volume 73,
Issue 1,
1990,
Page 73-81
Isabelle Murat,
Patrick Lechene,
Renée Ventura-Clapier,
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摘要:
Volatile anesthetics were demonstrated to decrease calcium sensitivity and maximal developed force of detergent-treated rat cardiac skinned fibers. To further investigate the possible mechanisms involved in the decrease of force production, stiffness measurements were performed at defined levels of activation with the use of quick length changes of 0.3 to 4% of initial muscle length in the absence and in the presence of 2 MAC of halothane, enflurane, or isoflurane. The results of various series of experiments suggest that these anesthetics have multiple sites of action on cardiac myofibrillar proteins: 1) they decreased active stiffness indicating a decreased number of attached force-generating cross-bridges; 2) they increased the stiffness/force ratio suggesting that the individual force developed by each cross-bridge was decreased during anesthetic exposure; and 3) they increased the time constant of force recovery, which is consistent with the decreased rate of ATP hydrolysis described by others. These changes in cross-bridges kinetics and efficiency may result from conformational changes in all the protein systems involved in force production, and especially actin–myosin attachment and detachment. However, the changes observed were small despite a relatively high concentration of anesthetics; therefore, they will probably participate only to a moderate extent in the overall negative inotropic effect of these agents.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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13. |
Isoflurane and Whole Body Leucine, Glucose, and Fatty Acid Metabolism in Dogs |
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Anesthesiology,
Volume 73,
Issue 1,
1990,
Page 82-92
Fritz Horber,
Sebastian Krayer,
John Miles,
Philip Cryer,
Kai Rehder,
Morey Haymond,
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摘要:
Following 4 h of general anesthesia with halothane [1.5 minimum alveolar concentration (MAC)]-nitrous oxide (50% in oxygen), whole body protein synthesis is decreased and the rate of leucine oxidation is increased in dogs. To evaluate the effects of general anesthesia with isoflurane on whole body fuel metabolism and the effects of duration of anesthesia on these processes, eight dogs were studied, once in the conscious state (over 9 h) and again prior to and during isoflurane anesthesia (1.5 MAC) for 3.5 h (n = 8). Three additional dogs were studied in the conscious state and over 5 h of anesthesia. Changes in protein, fatty acid, and glucose metabolism were estimated using isotope dilution techniques, employing simultaneous infusions of L-[1-14C]leucine, [6-3H]glucose and [9,10-3H]palmitate. Ten minutes after the beginning of the administration of isoflurane, total leucine carbon flux, leucine oxidation, and leucine incorporation into proteins decreased (P< 0.05), resulting in a slight decrease in the ratio of leucine oxidation to nonoxidative leucine disappearance (LOX/NOLD,P< 0.05), an indicator of leucine catabolism. Throughout the 5 h of anesthesia, whole body protein synthesis remained decreased (P< 0.01), whereas leucine flux and oxidation increased progressively throughout the remainder of the study, resulting in a more than 80% increase in the ratio of LOX/NOLD. After 10 min of isoflurane anesthesia, both plasma free fatty acid concentrations and palmitate turnover had decreased by more than 70% (P< 0.001) and remained suppressed (P< 0.001) throughout the remainder of the anesthesia, consistent with decreased lipolysis. Glucose production was increased 10 min (P< 0.05) following induction of anesthesia and peripheral glucose utilization was decreased following 3.5 h of isoflurane anesthesia (P< 0.05). These data strongly suggest a widespread and immediate metabolic effect of isoflurane anesthesia, which includes peripheral insulin resistance to glucose disposal, decreased lipolysis, and a progressive increase in protein wasting with increasing duration of anesthesia.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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14. |
The Nonlinear Potency of Sub‐MAC Concentrations in Nitrous Oxide in Decreasing the Anesthetic Requirement of Enflurane, Halothane, and Isoflurane in Rats |
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Anesthesiology,
Volume 73,
Issue 1,
1990,
Page 93-99
Daniel Cole,
Michael Kalichman,
Harvey Shapiro,
John Drummond,
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摘要:
The effect of nitrous oxide (N2O) on the MAC of enflurane, halothane, and isoflurane was determined in male rats. Each rat received either enflurane, halothane, or isoflurane, along with 0%, 15%, or 75% N2O. Anesthetic equilibration was verified by mass spectrometry sampling of end-tidal gases. MAC was determined at each N2O concentration by the standard tail clamp method. The N2O dose–response data for each animal were fit by a second-order polynomial equation to estimate the value of a second-order coefficient. A linear dose–response would result in a value of zero, whereas the extent to which the data deviate from nonlinearity would be reflected by an increase in the value of this coefficient. The null hypothesis, that the second-order coefficient should be zero, was tested by a one-sample two-tailedttest. The volatile anesthetic requirement decreased as the N2O concentration increased; however, it did not do so linearly. For each of the three volatile anesthetic groups, the second-order coefficients were consistently greater than zero (P< 0.05). These data are not consistent with the accepted presumption that the summation of N2O with volatile anesthetics is linear.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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15. |
Isoflurane and Halothane Attenuate Coronary Artery Constriction Evoked by Serotonin in Isolated Porcine Vessels and in Intact Pigs |
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Anesthesiology,
Volume 73,
Issue 1,
1990,
Page 100-108
T. Witzeling,
J. Sill,
J. Hughes,
G. Blaise,
M. Nugent,
D. Rorie,
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摘要:
Serotonin is a vasoconstrictor thought to cause coronary artery constriction in humans. The purpose of this study was to determine if isoflurane and halothane each attenuate coronary artery constriction evoked by serotonin in pigs. Bothin vitroandin vivoexperimental methods were used. Isolated coronary arteries with and without endothelium were studied in organ chambers in the presence and absence of 2.5% concentrations of the anesthetics. In intact pigs serotonin was infused directly into the left anterior descending coronary arteries to induce constriction. The vasodilator effects of 0.5%, 1.25%, and 2.0% isoflurane and halothane were determined using quantitative angiography. Contractile responses of isolated coronary arteries were depressed by the two anesthetics. Maximum contractile responses to serotonin were as follows: rings with endothelium 45 ± 5% untreatedversus29 ± 5% with isoflurane 2.5% (difference between dose-response curves,P< 0.01) and without endothelium 67 ± 5% untreatedversus51 ± 6% with isoflurane 2.5% (P< 0.001); with endothelium 52 ± 7% untreatedversus28 ± 7% with halothane 2.5% (P< 0.001) and without endothelium 65 ± 5% untreatedversus40 ± 6% with halothane 2.5% (P< 0.001). In intact pigs isoflurane and halothane dilated constricted coronary arteries with and without endothelium at all anesthetic concentrations tested, including concentrations as low as 0.5%. Isoflurane 1.25% increased diameter of vessels with endothelium from 1.5 ± 0.1 mm to 1.7 ± 0.1 mm (P< 0.02) and halothane 1.25% increased diameter from 1.6 ± 0.1 mm to 1.7 ± 0.1 mm (P< 0.01). In vessels without endothelium isoflurane 1.25% increased diameter from 1.8 ± 0.1 mm to 2.0 ± 0.1 mm (P< 0.01) and halothane 1.25% increased diameter from 1.9 ± 0.1 mm to 2.0 ± 0.2 mm (P< 0.01). Results demonstrate that isoflurane and halothane attenuate contractile responses evoked by serotonin in pig coronary arteries studied bothin vitroandin vivo.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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16. |
The Effects of Extracellular Magnesium on Myoplasmic [Ca2+] in Malignant Hyperthermia Susceptible Swine |
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Anesthesiology,
Volume 73,
Issue 1,
1990,
Page 109-117
J. Lopez,
V. Sanchez,
I. Lopez,
J. Ryan,
M. Mendoza,
F. Sreter,
P. Allen,
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摘要:
It is now well established that the pathophysiology of the malignant hyperthermia (MH) syndrome is related to a malfunction of intracellular calcium homeostasis. Magnesium plays important roles in the basic contractile properties of muscle, and many of its actions are antagonistic to those of calcium. The aim of this study was to determine the effectiveness of magnesium sulphate to prevent the MH episode in susceptible animals and correlate this with its effects on the intracellular free calcium ([Ca2+]i). The experiments were carried out using six control (Yorkshire) and ten MH-susceptible crossbred swine (Poland China X Pietrain). After determination of resting concentrations of [Ca2+]iand [Mg2+]i, each animal was given either two iv bolus doses of 50 mg/kg or one iv bolus of 100 mg/kg of MgSO4. The resting [Ca2+]iand [Mg2+]iwere determined by means of ion-selective microelectrodes. The resting [Ca2+]iin normal muscle fibers was 0.11 ± 0.01 μM (mean ± SEM), whereas in the MH muscles the resting [Ca2+]iwas 0.36 ± 0.01 μM. In neither group was the resting [Ca2+]imodified by MgSO4. This cumulative dose of MgSO4(100 mg/kg) was not able to prevent the induction of an MH episode by 2% halothane. Although MgSO4did not directly decrease [Ca2+]i, it did attenuate the increase in [Ca2+]iassociated with the syndrome from 7.29 ± 0.43 μM in untreated animals to 0.84 ± 0.03 μM in MgSO4pretreated swine. In addition, the limb rigidity that accompanies this increase in calcium was prevented by MgSO4pretreatment. Baseline measurements of [Mg2+]iwere not different in control and MH-susceptible muscles. Administration of MgSO4(100 mg/kg) increased [Mg2+]i1.8-fold (P< 0.001). These results indicate that MgSO4by itself was ineffective both in decreasing resting [Ca2+]iand in preventing the changes associated with the MH episode. However, MgSO4was able to quantitatively reduce the increase in [Ca2+]i, prevent the limb rigidity, and reduce the increment in body temperature usually associated with the clinical syndrome.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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17. |
Effects of Ketamine, Halothane, Enflurane, and Isoflurane on Systemic and Splanchnic Hemodynamics in Normovolemic and Hypovolemic Cirrhotic Rats |
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Anesthesiology,
Volume 73,
Issue 1,
1990,
Page 118-124
Bertrand Debaene,
Gérard Goldfarb,
Alain Braillon,
Pierre Jolis,
Didier Lebrec,
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摘要:
The effects of ketamine, halothane, enflurane, and isoflurane on systemic and splanchnic hemodynamics in cirrhotic rats that were either normovolemic or hypovolemic following hemorrhage were characterized. Rats received at random either ketamine (30 mg/kg iv, 1.5 mg · kg-1· min-1iv), halothane, enflurane, or isoflurane (1 MAC). Conscious rats were considered the control group. Four weeks before hemodynamic studies bile duct ligation was performed in all rats to induce cirrhosis. Hemodynamic measurements were performed using the radioactive microsphere method 1 h after the onset of anesthesia and 30 min after hemorrhage. Anesthetized rat lungs were mechanically ventilated with room air. Before hemorrhage cardiac index was higher in conscious rats and in rats receiving isoflurane than in the other groups (P< 0.001). Hepatic arterial blood flow was similar in conscious rats and in those receiving isoflurane or halothane and was higher than in those receiving ketamine or enflurane. The lowest splanchnic and portal venous tributary blood flows were observed in rats receiving enflurane. After hemorrhage cardiac index was significantly less than before hemorrhage in all groups, except in rats receiving enflurane. After hemorrhage portal venous tributary blood flow decreased significantly in all groups except in enflurane group. During halothane and enflurane anesthesia hepatic arterial blood flow and hepatic arterial fraction of cardiac output decreased (P< 0.01) and they were maintained in the other groups. After hemorrhage hepatic arterial fraction of cardiac output in conscious rats was higher than in those receiving ketamine, halothane, or enflurane (P< 0.05) and was similar to those receiving isoflurane. Thus, halothane inhibited the increase of hepatic arterial blood flow, whereas it was maintained under isoflurane as in normals. Furthermore, in normovolemic cirrhotic rats hepatic arterial blood flow was preserved only during halothane and isoflurane. After hemorrhage among the agents and doses studied, isoflurane seems the most efficient for preserving splanchnic circulation in hypovolemic cirrhotic rats.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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18. |
The Cerebral Functional, Metabolic, and Hemodynamic Effects of Desflurane in Dogs |
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Anesthesiology,
Volume 73,
Issue 1,
1990,
Page 125-131
Lon Lutz,
James Milde,
Leslie Milde,
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摘要:
The effects of 0.5–2.0 MAC (3.6–15%) desflurane on cerebral function, metabolism, and hemodynamics and on systemic metabolism and hemodynamics were examined in dogs. Desflurane produced a significant dose-related decrease in cerebral vascular resistance from 1.53 ± 0.21 mmHg · ml-1· min · 100 g at 0.5 MAC to 0.50 ± 0.03 mmHg · ml-1· min · 100 g at 2.0 MAC desflurane. This was accompanied by an increase in cerebral blood flow (CBF) from 61 ± 7 ml · min-1· 100 g-1at 0.5 MAC to 78 ± 3 ml · min-1· 100 g-1at 1.5 MAC desflurane. At 2.0 MAC desflurane CBF was 52 ± 2 ml · min-1· 100 g-1but was associated with a decrease in mean arterial pressure (MAP) to 43 ± 2 mmHg. When MAP was increased to 73 ± 3 mmHg with phenylephrine, CBF increased to 87 ± 3 ml · min-1· 100 g-1at this concentration. At 0.5 MAC desflurane, intracranial pressure (ICP) was 15 ± 5 mmHg, higher than normal, but did not change significantly with increasing concentrations of desflurane. Increasing concentrations of desflurane initially produced on the EEG the common pattern sequence of increasing depth of anesthesia with decreasing frequency and increasing amplitude progressing to burst suppression and then at 2.0 MAC desflurane to regular attenuation with interruption by periodic polyspiking, a pattern similar to that seen with isoflurane. At both 1.5 and 2.0 MAC the EEG pattern initially observed at that concentration changed to one with faster background activity with time. In parallel with changes observed on EEG desflurane produced a significant decrease in the cerebral metabolic rate for oxygen to 2.52 · 0.1 ml · min-1· 100 g-1at 2.0 MAC, which is comparable to that produced by other anesthetics. Cerebral metabolites measure at the end of the study were within normal limits. Desflurane produced a dose-related decrease in mean arterial pressure from 114 ± 5 mmHg at 0.5 MAC to 43 ± 2 mmHg at 2.0 MAC due primarily to a significant decrease in systemic vascular resistance. Only at 2.0 MAC was there a significant decrease in cardiac index, which may also have contributed to the decreased MAP at this concentration. Increasing doses of desflurane had no effect on heart rate or whole body oxygen consumption. It is concluded that desflurane is a cerebral vasodilator similar to that of the other volatile anesthetics and a cerebral metabolic suppressant similar to isoflurane. It differs from the other anesthetics in that the effect of higher concentrations of desflurane on EEG activity may be limited with time.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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19. |
Pulmonary Reactivity to Methacholine during β‐adrenergic BlockadePropranololversusEsmolol |
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Anesthesiology,
Volume 73,
Issue 1,
1990,
Page 132-136
Joseph Tobias,
Russell Sauder,
Carol Hirshman,
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摘要:
Pulmonary reactivity to methacholine after equipotent β-blocking doses of propranolol and esmolol was compared in seven basenji-greyhound dogs during thiopental–fentanyl anesthesia. Equipotent doses of esmolol and propranolol were determined by both heart rate effects and by isoproterenol response curves. Propranolol (2 mg/kg) was administered intravenously as a bolus dose and esmolol (0.4–0.5 mg · kg-1· min-1) was administered by continuous infusion. Both esmolol and propranolol significantly decreased heart rate and mean arterial pressure (P< 0.001). Baseline pulmonary resistance and dynamic compliance did not change after the administration of either propranolol or esmolol. However, propranolol significantly shifted the methacholine dose-response curve to the left so that methacholine (0.3 mg/ml) increased pulmonary resistance by 7.9 ± 0.97 cmH2O · I-1· s-1(mean ± SEM of seven dogs) after pretreatment with propranolol but only 4.4 ± 0.89 cmH2O · I-1· s-1(P< 0.05) without propranolol pretreatment (control). Esmolol, however, did not significantly shift the methacholine dose-response curve. Methacholine (0.3 mg/ml) increased resistance 4.0 ± 0.89 cmH2O·I-1· s-1during esmolol administration. This study shows that at equipotent β1-blocking doses, propranolol, but not esmolol, produces significant increases in pulmonary reactivity to methacholine.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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20. |
Developmental Changes in Effects of Halothane and Isoflurane on Contractile Properties of Rabbit Cardiac Skinned Fibers |
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Anesthesiology,
Volume 73,
Issue 1,
1990,
Page 137-145
Isabelle Murat,
Jacqueline Hoerter,
Renée Ventura-Clapier,
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摘要:
Immature hearts of various animal species and humans have been demonstrated to be more sensitive than adult hearts to the myocardial depressant effects of volatile anesthetics. To further investigate the mechanisms involved, the calcium sensitivity and maximal activated tension of detergent-treated left ventricular fibers of fetuses (30 days), newborn (1-day-old), immature (3-, 8-, and 17-day-old), and adult rabbits were determined by stepwise exposure to increasing Ca2+concentrations. Responses were measured prior to and after exposure to equianesthetic concentrations of halothane (1%) or isoflurane (1.5%) applied in a random order. In control conditions maximal developed tension was the lowest in fetuses (11.1 ± 0.6 mN · mm-2), intermediate in newborn and immature rabbits, and highest in adults (25.6 ± 2.9 mN · mm-2). There were also age-related changes in calcium sensitivity; pCa (= -log10[Ca2+]) for half-activation (pCa50) was significantly less in 1-, 3-, and 8-day-old rabbits (5.444 ± 0.036, 5.425 ± 0.017, and 5.385 ± 0.019, respectively) than in adults (5.517 ± 0.010), whereas it was not different in fetuses (5.521 ± 0.017). During anesthetic exposure both calcium sensitivity and maximal developed tension decreased significantly in all age groups of animals, with both anesthetics having a similar effect in animals of identical age. However, calcium sensitivity decreased significantly more in newborn animals (0.192 and 0.196 pCa unit for halothane and isoflurane, respectively) compared with adults (0.122 and 0.137 pCa units, respectively). By contrast, fetuses were less sensitive to the myocardial depressant effects of anesthetics than were newborn animals. The results of this study are consistent with the hypothesis of a greater sensitivity of contractile apparatus of neonatal heart to the depressant effects of volatile anesthetics. This could be related to developmental changes that are known to affect the contractile proteins, especially the troponin-tropomyosin system.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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