ISSN:0003-3022    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The population pharmacokinetic parameters describing the plasma concentrationversustime profile of alfentanil in patients undergoing general anesthesia were determined from 614 plasma concentration measurements collected in four previously reported studies with a total of 45 patients. A nonlinear regression analysis evaluating the effect of six concomitant variables revealed a significant influence of body weight on the volume of the central compartment (Vc), and a decrease with age of total body clearance (CL) and of redistribution rate from the deep compartment (k31). A small but significant effect of sex on the Vcwas also observed. The duration of anesthesia and the concomitant administration of inhalational anesthetics had no effect on alfentanil pharmacokinetic parameters. The mean CL and Vcfor alfentanil in a 70-kg male, aged less than 40 yr, were estimated as 0.356 1/min and 7.77 1, respectively. After correction for age, body weight, and sex, the remaining interindividual variability of alfentanil kinetics (expressed as coefficient of variation) was 48% for CL and 33% for Vc. These population pharmacokinetic parameter estimates should increase the accuracy of predicting concentration-time profiles for intravenous alfentanil infusions. A computer program is presented that allows prediction of the alfentanil plasma concentration and the 68% interval limits of the prediction from the study data analysis.

ISSN:0003-3022    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The pharmacokinetics of alfentanil have been studied in eight children aged between 4 and 8 yr and five adults during general anesthesia. All patients were given 20 μg/kg alfentanil as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 6 h by radioimmunoassay. Plasma protein binding was measured by equilibrium dialysis using tritiated alfentanil. The optimal pharmacokinetic model for alfentanil was an open two-compartment model. Total apparent volume of distribution (Vdas) was 457 ± 160 ml/kg in adults and 163 ± 110 ml/kg in children (P< 0.01). When recalculated by surface area Vdaswas still decreased in children (P< 0.01). Plasma clearance (Cl) was similar in the two groups. Terminal elimination half-life was significantly shorter in children (40 ± 9 min) than in adults (97 ± 22 min;P< 0.01). The shorter elimination half-life could be due to the smaller total apparent volume of distribution in children. Plasma protein binding was comparable between children and adults and could not explain the smaller volume of distribution in children. It is suggested that the smaller volume of distribution of alfentanil in children is a result of the decreased percentage of fat tissue in children.

ISSN:0003-3022    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Deerased urinary output (&OV0622;uml/min) after institution of PEEP is attributed to a variety of mechanisms including decreased cardiac output and renal blood flow (RBF), activation of neurohormonal reflexes, increased catecholamines, plasma renin activity (PRA), and antidiuretic hormone (ADH) release. To evaluate these factors, seven normovolemic patients (36 yr ± 13 SD), free of preexisting lung, cardiac, or renal disease, requiring continuous mandatory ventilation for neurologic reasons were studied. The authors measured or calculated: total blood volume (TBV) (51Cr); right atrial, pulmonary arterial, pulmonary wedge, and systemic pressures, cardiac index (CI); renail plasma flow (RPF) (iodohippurate sodium131I [131I PAH] clearance); glomerular filtration rate (GFR) (creatinine clearance), free water clearance (ĊH2O), osmolal clearance (Ċosm), fractional excretion of sodium (FENa+) and potassium (FEK+); and plasma renin activity (PRA) (ng·ml−1· h−1), plasma ADH (pg/ml; radioimmunoassay), epinephrine (E in pg/ml), and norepinephrine (NE in pg/ml) (double-isotope radioenzymatic assay). Two conditions were studied after 90-min steady state: 1) zero PEEP (ZEEP); and 2) 15 cmH2O PEEP. PEEP caused a significant decrease in CI (-21%;P< 0.01) and RPF (-19%;P< 0.05) without significant decrease in GFR. A significant decrease in &OV0622;u(-55%;P< 0.05), FENa+(-39%;P< 0.05) and Ċosm(-36%;P< 0.25) occurred without modification in ĊH2O. Plasma ADH remained in the normal range and did not increase when PEEP was applied. NE increased significantly (P< 0.05) in parallel with PRA (r = 0.80;P< 0.01). Within the limits of this study, acute antidiuresis during PEEP ventilation appears to result from systemic and renal hemodynamic changes with simultaneous sympathetic activation and high PRA. Moreover, at constant plasma osmolality and TBV, ADH remained in the normal low range. This study demonstrates the absence of any ADH release during PEEP-induced antidiuresis.

ISSN:0003-3022    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Three weeks after dosing male Fischer 344 rats with streptozotocin to induce diabetes, enflurane was administered ip, and 1 h later, fluoride levels were measured in plasma and livers were removed. Hepatic microsomes were prepared, and the oxidative defluorination of enflurane, isoflurane, and methoxyflurane and the reductive defluorination of halothane were measuredin vitro.In diabetic rats the defluorination of enflurane was increased 3.4-fold over control levelsin vivoand 2.7-foldin vitro.Insulin treatment prevented these effects. In vitro, metabolism of isoflurane by livers from diabetic rats was 2.5-fold greater than by livers from control rats, but defluorination of methoxyflurane and of halothane was not altered. The results show that streptozotocin-induced diabetes in rats enhances the defluorination of enflurane and of isoflurane but not of methoxyflurane or halothane.

ISSN:0003-3022    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The effect of isoflurane on median nerve somatosensory evoked potentials (MN-SSEPs) was studied in 15 patients. Anesthesia was induced with thiamylal and maintained with oxygen and isoflurane. MN-SSEPs were recorded in awake patients and after achieving 0.5, 1.0, 1.5, and 2.0% stable end-tidal concentrations of isoflurane. Peak latencies and amplitudes of EP-N13, and N20 and conduction times EP-N13, N13-N20, and EP-N20 were measured. Peak latencies of all components increared after all concentrations of isoflurane compared with control values. N20 peak latencies after 1% and 1.5% isoflurane differed significantly, whereas EP and N13 latencies showed no significant difference. No significant change in conduction time EP-N13 resulted from 1% and 1.5% concentrations of isoflurane compared with control values. Isoflurane increased conduction time N13-N20 significantly when compared with control values, and this increase was dose related. Amplitude of EP and N13 did not show significant change with 1% and 1.5% isoflurane when compared with control values. Amplitude of N20 decreased significantly following isoflurance anesthesia compared with control values, and the difference between 1% and 1.5% isoflurane recordings was also statistically significant. N20 was not discernible in one out of 14 patients after 1.5% and in three out of ten patients after 2% isoflurane. These results indicate that subcortical potentials are less affected by isoflurane anesthesia than cortical potentials. Amplitude reduction of cortical potentials was more noticeable than either prolongation of peak latency or conduction time. The data suggest that in surgical procedures involving cervical spinal cord, intraoperative monitoring of MN-SSEPs is possible even with high concentrations of isoflurane, as N13 can be reliably monitored. In procedures placing brain stem or cerebral somatosensory pathways at risk, where N20 needs to be monitored, high concentrations of isoflurane should be avoided.

ISSN:0003-3022    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Propanolol reduces the clearance of lidocaine by both reducing hepatie blood flow and inhibiting lidocaine metabolism. The authors investigated the possibility that propranolol reduces the clearance of bupivacaine as well. Bupivacaine, 30–50 mg, was administered intravenously to six normal human volunteers, over 10–15 min on two occasions, at least 2 weeks apart. Propranolol, 40 mg orally every 6 h, was used on one occasion, beginning 24 h prior to the bupivacaine administration. The sequence of the sessions was randomized. Twenty-two venous blood samples were obtained over 36 h in order to determine bupivacaine clearance, terminal elimination rate constant, and volume of distribution. All subjects experienced mild CNS toxicity, consisting of tinnitus, facial tingling, or subtle visual disturbances, associated with peak venous plasma concentrations of 0.81 to 2.7 μg/ml. Mean bupivacaine clearance was 0.33 ± 0.12 1/min for the control session and 0.21 ± 0.12 1/min during propranolol use, a significant 35% reduction (P< 0.01). The terminal elimination rate constant (beta) was 0.27 ± 0.16 h−1for the control session and 0.14 ± 0.069 h−1with propranolol (P< 0.05); terminal elimination half-lives were 2.6 and 4.9 h, respectively. Volume of distribution was unchanged. Because bupivacaine clearance should be relatively insensitive to hepatic perfusion, it appeared that propranolol caused a substantial inhibition of bupivacaine metabolism at the level of the hepatocyte. These data suggest that concomitant use of propranolol could result in the accumulation of a toxic concentration of bupivacaine.

ISSN:0003-3022    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The hypothesis that iv dextrose infusion prior to—and head position during—cerebral ischemia would influence the severity and pattern of neurologic injury was tested in primates. Fifteen pigtail monkeys weighing 3.3 ± 0.2 kg (mean ± SE) were subjected to 17 min complete cerebral ischemia followed by 24 h intensive care treatment and neurologic assessment for an additional 72 h. Monkeys were given 50 mlivinfusions of either dextrose 5% in 0.45% saline solution (n =8) or lactated Ringer's solution (n = 7) during the preparatory period. This volume corresponds to approximately 1 1/70 kg individual. These same monkeys were placed in either the lateral (n = 3), prone (n = 5), or supine (n = 7) position during the ischemic period. Two monkeys failed to meet preestablished protocol criteria and were excluded from data analysis. Blood glucose immediately preischemia in the dextrose-treated group (181 ± 19 mg · dl−1) was not significantly greater than in the group given lactated Ringer's solution (140 ± 6 mg · dl−1;P= 0.07). Dextrose infusion resulted in significantly greater cerebral injury at 96 h postischemia when comparing both neurologic (P< 0.05) and histopathology (P< 0.05) scores. Specifically, dextrose administration resulted in the greatest injury to the insular cortex, thalamus, Purkinje cells, and substantia nigra. Although blood glucose was <250 mg · dl−1in all monkeys at the time of complete cerebral ischemia, there was a high correlation between blood glucose rank and neurologic function rank (ra= 0.76;P< 0.005). The authors were unable to note any effect of head position on the distribution of histopathologic lesions. Prior to removing the brain for histopathologic studies, four monkeys were given repeat infusions of 50 ml dextrose 5% in 0.45% saline solution over 11 ± 1 min. These infusions produced increases in blood glucose from 56.7 ± 7.6 to 244 ± 24.9 mg · dl−1(P< 0.01) and increases in brain glucose from 1.64 ± 0.22 to 5.11 ± 0.48 μmol · g−1(P< 0.01).

ISSN:0003-3022    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The pulmonary hemodynamic response to dopamine and to dobutamine was investigated in dogs ventilated with hyperoxia (fraction of inspired O2concentration [FIO2], 0.4 balance nitrogen) and challenged with short periods of inspiratory hypoxia (FIO20.125 or 0.1 for 10 min). Dopamine at doses of 5, 10, and 20 μg · kg−1· min−1(n = 7 dogs) increased cardiac index (CI) and pulmonary artery pressure (PAP) without change in indexed pulmonary vascular resistance (PVRI) at both FIO20.4 and 0.125. Hypoxia-induced increases in PVRI were unaffected by dopamine. Dobutamine at doses of 5, 10, and 20 μg · kg−1· min−1(n = 7 dogs) increased CI, with an increase in PAP without change in PVRI at FIO20.4, and at FIO20.125 there was no change in PAP and a decrease in PVRI. Hypoxia-induced increases in PVRI were inhibited by dobutamine, partially at 5 and 10 μg · kg−1· min−1, and completely at 20 μg · kg−1· min−1. In two additional groups of seven dogs the effects of reducing FIO2from 0.4 to 0.1 without and with dopamine or dobutamine either at 10 μg · kg−1· min−1(n = 7) or at 20 μg · kg−1· min−1(n = 7) were studied at an unchanged CI obtained by stepwise inflations of a balloon placed in the inferior vena cava. At constant flow both amines increased PVRI at FIO20.4 and did not significantly affect hypoxia-induced increases in PVRI. It is concluded that at doses up to 20 μg · kg−1· min−1, dopamine and dobutamine have similar effects on the pulmonary circulation of intact animals. Neither amine seems directly to inhibit hypoxic pulmonary vasoconstriction.

ISSN:0003-3022    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The Meyer-Overton role has been interpreted to mean that general anesthetics act at a nonpolar site, either in a lipid bilayer or a protein. Optical isomers, also called enantiomers, are pairs of compounds with the same molecular formula and functional groups, but which differ in the arrangement of the groups around an “asymmetric” carbon atom and in the direction they rotate plane-polarized light. By definition, enantiomers that are anesthetics can distinguish between stereoselective and nonselective sites of anesthetic action. We used such enantiomers to determine whether anesthetics are stereoselective in their actions on animals by measuring the potencies of a homologous series of secondary aliphatic alcohols from 2-butanol through 2-octanol in tadpoles, using reversible loss of righting reflex as the endpoint. None of the isomeric pairs exhibited significant differences in potency. Anesthetic potency increased logarithmically with the number of carbon atoms in the hydrocarbon chain of the alcohol. The ED50± SE (mM) for the (+) and (-) forms of the alcohols, respectively, were as follows: 2-butanol 17 ± 1.2, 17 ± 1.1: 2-pentanol 4.7 ± 0.28, 4.8 ± 0.27; 2-hexanol 1.33 ± 0.068, 1.42 ± 0.079; 2-heptanol 0.32 ± 0.011, 0.33 ± 0.020; and 2-octanol 0.063 ± 0.0042, 0.061 ± 0.0032. These data demonstrate a lack of stereo-selectivity in the interactions between the anesthetic secondary alcohols and their site of action in animals.

ISSN:0003-3022    

出版商:OVID    

年代:1987

数据来源: OVID