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11. |
Tolerance and Dependence in Neonates Sedated with Fentanyl during Extracorporeal Membrane Oxygenation |
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Anesthesiology,
Volume 73,
Issue 6,
1990,
Page 1136-1140
John Arnold,
Robert Truog,
E. Orav,
Joseph Scavone,
Marc Hershenson,
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摘要:
We undertook a retrospective chart review of 37 neonates who received fentanyl by continuous infusion while undergoing extracorporeal membrane oxygenation (ECMO) between May 1986 and October 1988. We quantified the doses of all sedatives utilized, determined the Incidence of neonatal abstinence syndrome (NAS), and identified risk factors associated with NAS. We determined peak fentanyl Infusion rate, mean fentanyl infusion rate, total fentanyl dose, and duration of ECMO therapy. NAS was observed in 21 of 37 neonates (57%). In both the NAS and non-NAS neonates, mean infusion rate increased steadily during ECMO therapy, from a mean of 11.6 ± 6.9 (SD) μ.kg−1.h−1on day 1 to a mean of 52.5 ± 19.4 (SD) μ.kg−1.h−1by day 8. Total fentanyl dose and duration of ECMO were significantly greater in neonates with NAS. We found that neonates with a total dose > 1.6 mg/kg or an ECMO duration > 5 days had a significantly greater incidence of NAS (chi-squared test,P< 0.01 andP< 0.005; odds ratios = 7.0 and 13.9, respectively). With multiple logistic regression, ECMO duration was found to be the most powerful predictor of the occurrence of NAS. We also measured plasma fentanyl concentrations in a separate group of 5 neonates receiving fentanyl by continuous infusion for sedation. Fentanyl concentrations increased steadily during the period of infusion, suggesting the development of tolerance to the sedating effects. We conclude that continuous administration of fentanyl for sedation is associated with the uniform development of tolerance and a significant Incidence of dependence. Alternative approaches to sedation should be investigated.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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12. |
Differential Cross‐tolerance Between Intrathecal Morphine and Sufentanil in the Rat |
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Anesthesiology,
Volume 73,
Issue 6,
1990,
Page 1141-1147
Maurice Sosnowski,
Tony Yaksh,
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摘要:
By means of a subcutaneously implanted osmotic pump, groups of rats received a constant-rate (1 μ1/h), 7-day Intrathecal Infusion of saline or one of twomuopioid agonists: sufentanil (0.6 nmol/h) or morphine (20 nmol/h). These concentrations of morphine and sufentanil yielded a comparable near maximal hot-plate response latency on day 1 of the infusion. On day 7, the magnitude of tolerance was assessed to each group by establishing intrathecal dose-response curves and ED50values for sufentanil and morphine given as a bolus injection. Each infused animal was used for a single bolus injection. In all cases, infusion with the opioid resulted in a rightward shift (increase in ED50) for both morphine and sufentanil as compared to saline-infused animals. The magnitude of the shift, however, was different for the two drugs. Thus in morphine-infused rats, the morphine ED50increased as compared to saline-infused animals by a factor of 44, whereas the sufentanil ED50shifted by a factor of 10. In sufentanil-infused animals, the respective shifts in the morphine and sufentanil ED50values were increased by a factor of 9 and 3, respectively. Thus, a significantly greater shift as compared to saline-infused animals was observed in morphine-infused than in sufentanil-infused animals. Conversely, regardless of the opioid to which the animal was exposed, morphine-tested animals showed a greater rightward shift than did sufentanil-tested animals. These data showing a nonsymmetric tolerance between agents acting at the samemureceptor are consistent with the argument that these two agents differ in efficacy,i.e., the fraction of the receptor population each must occupy to produce a given effect. Agents with high efficacy and a significant receptor reserve (e.g., sufentanil) will down-regulate fewer receptors than will agents with low efficacy and a smaller receptor reserve (e.g., morphine). As a result, agents with higher efficacy at a receptor show theoretically less tolerance over time as compared with less efficacious agents acting at the same receptor.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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13. |
Effects of Nitrous Oxide on Myocardial Contractility as Evaluated by the Preload Recruitable Stroke Work Relationship in Chronically Instrumented Dogs |
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Anesthesiology,
Volume 73,
Issue 6,
1990,
Page 1148-1157
Paul Pagel,
John Kampine,
William Schmeling,
David Warltier,
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摘要:
Assessment of the effects of nitrous oxide on myocardial contractile functionin vivohas been complicated by lack of a reliable, easily quantified, load-independent index of contractility and by the presence of intact autonomic nervous system reflexes. Although several previous investigations in humans and experimental animals have demonstrated that nitrous oxide possesses direct negative inotropic effects, this conclusion remains controversial. This investigation reexamined the effect of nitrous oxide on myocardial contractile function when this agent was combined with baseline isoflurane or sufentanil anesthesia in chronically instrumented dogs. Contractility was evaluated with the use of the regional preload recruitable stroke work (PRSW)-end-diastolic segment length relationship, a method that provides an accurate, relatively afterload-independent assessment of inotropic state in conscious and anesthetized dogs. Because autonomic nervous system tone may influence the response of systemic hemodynamics to anesthesiain vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Two groups of experiments, consisting of a total of 15 experiments, were performed with 12 dogs. Dogs, chronically instrumented for measurement of systemic hemodynamics, including left ventricular pressure and subendocardial segment length, were anesthetized with isoflurane or sufentanil. Thirty percent and 70% nitrous oxide were then administered in a random fashion. Left ventricular pressure-segment length loops were generated after 30 min of equilibration after each anesthetic intervention with the use of preload reduction by partial inferior vena caval constriction, and regional PRSW was calculated. Regional PRSWversusend-diastolic length slope reflected decreases in contractile state when nitrous oxide was added to isoflurane (50 ± 5 for isoflurane alone to 28 ± 2 erg.cm−1.10-3.mm−1with 70% added nitrous oxide) or sufentanil (73 ± 8 for sufentanil alone to 52 ± 5 erg.cm-2.10-3.mm−1with 70% added nitrous oxide). Similar decreases in left ventricular positive dP/dtw were observed as well, reflecting decreases in contractile function. The results further suggest that the degree of functional depression produced by nitrous oxide is nearly equal when isoflurane and sufentanil groups are compared. This study demonstrates that nitrous oxide possesses direct negative inotropic actions independent of changes in autonomic nervous system tone in the chronically instrumented dog.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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14. |
A Comparison of the Effects of Halothane and Tetrodotoxin on the Regional Repolarization Characteristics of Canine Purkinje Fibers |
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Anesthesiology,
Volume 73,
Issue 6,
1990,
Page 1158-1168
Lawrence Turner,
Jure Marijic,
John Kampine,
Zeliko Bosnjak,
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摘要:
The effect of halothane, tetrodotoxin (TTX), veratridine (VTD), and alterations of extracellular calcium ion concentration ([Ca++]0) on regional difference of canine Purkinje fiber action potential duration (APD50and APD90) were investigatedin vitroat a paced rate of 75 beats per min. Under control conditions (n = 15 heart) APD90of proximal (false tendon) fibers (289 ± 6 ms) always exceeded (P< 0.01) that of distal (apical) fibers (213 ± 4 ms). Halothane (0.35–1.07 mM) reduced regional differences of APD90by producing dose-dependent decreases of proximal APD90without decreases of distal APD90. The regional actions of halothane were similar to those of low (0.33–1.0μM) concentrations of the Na+channel antagonist TTX, which also decreased proximal APD90more than distal APD90. The actions of halothane in combination with TTX further decreased proximal APD90, whereas the Na+channel agonist VTD, which increased proximal APD90more than distal APD90, reversed the regional actions of halothane. Decreasing Ca++influx by reducing [Ca++]0from 1.8 to 0.6 mM increased proximal APD90more than distal APD90in a manner opposite to the regional actions of halothane. Although there was no difference between the values of APD90obtained for each region in the presence of halothane at 0.6, 1.8, and 3.6 mm [Ca++]0, the action of halothane decreasing APD90of proximal fibers was more prominent at 0.6 mM [Ca++]0because of the increased APD90of fibers under this condition. The findings are consistent with, but do not definitively prove, the hypothesis that halothane may decrease APD90of proximal Purkinje fibers by a mechanism similar to that of TTX involving inhibition of plateauphase inward Na+current.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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15. |
The Inhibitory Action of Halothane on Reflex Constriction in Mesenteric Capacitance Veins |
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Anesthesiology,
Volume 73,
Issue 6,
1990,
Page 1169-1178
Thomas Stekiel,
Keizaburo Ozono,
John McCallum,
Zeliko Bosnjak,
William Stekiel,
John Kampine,
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摘要:
Potent inhalational anesthetics depress autonomic reflex responses at multiple sites. Most studies emphasize cardiac chronotropk changes and changes in systemic blood pressure. Recently, active reflex venoconstriction of 500–1,000 μm O.D. mesenteric veins has been demonstrated. In the current study, the effects of halothane on the reflex responses of similar mesenteric veins were measured. Mesenteric vein diameter and intravenous pressure were measured in 500–1,000 μm O.D. veins from the mesentery of segments of terminal ileum externalizedin situfrom 27 New Zealand white rabbits anesthetized with alpha-chloralose. Mean arterial pressure was measured with femoral arterial cannulation, and heart rate was determined from the arterial pressure signal. In a separate group of six animals, sympathetic efferent nerve activity was measured from a postganglionic splanchnic nerve. Reflex venoconstriction and increases in mean arterial pressure and mesenteric vein pressure in response to bilateral carotid occlusion were attenuated by 0.5% and 1% inhaled halothane but not by superfusate equilibrated with 3% halothane. Decreases in mesenteric vein diameter and increases in mesenteric vein pressure in response to celiac ganglion stimulation were unaffected by both 0.5% inhaled halothane and superfusate equilibrated with 5% halothane. The bilateral carotid occlusion reflex-mediated increase in sympathetic efferent nerve activity was depressed by both 0.5% and 1% inhaled halothane. The effect of inhaled halothane on prestimulation baseline vein diameter was inconsistent. Superfusate equilibrated with 5% but not 3% halothane caused baseline venodilation. These results suggest a mechanism whereby control of venous tone is inhibited by halothane proximal to the postganglionic neuron. This could involve central or ganglionic inhibition.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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16. |
Subarachnoid Clonidine Reduces Spinal Cord Blood Flow and Glucose Utilization in Conscious Rats |
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Anesthesiology,
Volume 73,
Issue 6,
1990,
Page 1179-1185
Gregory Crosby,
Margaret Russo,
Michele Szabo,
Kenneth Davies,
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摘要:
The authors investigated the spinal blood flow and metabolic effects of subarachnoid clonidine in conscious rats prepared with chronically implanted subarachnoid catheters. For the blood flow experiments, rats received saline (n = 7) or clonidine 20 nmol (7 μg; n = 6), 100 nmol (27 μg; n = 5), or 400 nmol (107 μg; n = 7) intrathecally. Another group of rats received clonidine 400 nmol intravenously (n = 4). Spinal glucose utilization was measured in rats that received either saline (n = 5) or clonidine 100 nmol (n = 5) intrathecally. Spinal cord blood flow (SCBF) and glucose utilization were measured in five gray and three white matter areas of lumbar spinal cord 15 min after drag administration with the autoradiographic iodo-[14C]-antipyrine and 2-[14C)-deoxyglucose methods, respectively. Physiologic differences between the groups were minor. Rats in the blood flow experiments that received clonidine 100 nmol had a slightly lower arterial Po2level (70 ± 1vs.82 ± 3 mmHg;P< 0.05), whereas those in the glucose utilization group were mildly hypocarbic (Pco227 ± 1vs.32 ± 2 mmHg;P< 0.01) relative to control animals. Only animals that received 400 nmol clonidine intrathecally had significant analgesia, as assessed by the tail-flick test. One control animal for the metabolism experiments was technically unsatisfactory and was excluded from data analysis. Subarachnoid clonidine reduced both SCBF and glucose utilization. In spinal gray matter, the largest decreases in flow (32–44%)P< 0.01) occurred with 20 nmol clonidine, whereas flow decreased least (12–27%) with the 400-nmol dose. On the other hand, white matter blood flow decreased (17–39%) only at the two higher doses. Intravenous clonidine 400 nmol reduced SCBF to the same extent as the same dose administered intrathecally. At the single dose studied, subarachnoid clonidine reduced glucose utilization 11–42% in spinal gray and while matter, although the changes were significant in only five of eight areas. Neither the blood flow nor the glucose utilization changes were confined to areas of spinal cord known to contain high concentrations of alpha-2 receptors. These results indicate that, even at subanalgesic doses, subarachnoid clonidine reduces SCBF substantially and that the decrease is associated with, and perhaps caused partially by, a decrease in spinal metabolic rate. Accordingly, these data suggest that the blood flow and analgesic effects of clonidine occur by different mechanisms and support the hypothesis that spinal vasoconstriction may contribute to subarachnoid clonidine's ability to prolong spinal anesthesia.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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17. |
Halothane Alters the Oxygen Consumption‐Oxygen Delivery Relationship Compared with Conscious State |
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Anesthesiology,
Volume 73,
Issue 6,
1990,
Page 1186-1197
Peter Rock,
Charles Beattie,
Allyn Kimball,
Daniel Nyhan,
Bessie Chen,
David Fehr,
Stephen Derrer,
Stephen Parker,
Paul Murray,
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摘要:
The authors' objectives were as follows: 1) to characterize for the first time the relationship between whole body O2delivery (Do2) and O2consumption (Vo2in adult conscious dogs; and 2) to assess the effects of the inhalational anesthetic, halothane, on that relationship. Do2was varied over a wide range in chronically instrumented dogs by gradual inflation and deflation of a hydraulic occluder implanted around the thoracic inferior vena cava to alter venous return and cardiac output. Vo2was measured at different values of Do2in dogs in the folly conscious state and again during halothane anesthesia. A “binning‘’ technique indicated that halothane decreased Vo2(P< 0.01) at any given value of Do2over a broad range of Vo2. A twoline piecewise linear regression analysis technique indicated that halothane decreased (P< 0.01) the critical O2delivery (GOD) from 20 ± 3 to 10 ± 1 ml.kg−1.min−1and increased (P< 0.01) O2extraction at COD from 31 ± 3 to 40 ± 2% However, the Do2-Vo2plots measured in both conscious and halothane-anesthetized dogs did not exhibit a discrete discontinuity but rather were closely fit (correlation coefficient = 0.98) by an exponential equation of the following form:O2extraction = B1.(1 - exp (-Do2/B2))/Do2where B1 if the delivery-Independent estimate of Vo2and B2 is the “delivery constant,‘’i.e., the Do2associated with a Vo2equal to 63% of B1. Halothane decreased B1 (P< 0.01) from 5.3 ± 0.1 to 3.9 ± 0.1 ml. kg−1. min−1and decreased B2 (P< 0.01) from 5.6 ± 0.3 to 3.6 ± 0.3 ml.kg−1.min−1compared with that measured in conscious dogs. Thus, compared with the conscious state, halothane anesthesia alters the fundamental relationship between Do2and Vo2and may have a beneficial effect on tissue oxygenation at low values of Do2.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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18. |
Pharmacology of Intrathecal Adrenergic AgonistsCardiovascular and Nociceptive Reflexes in Halothane‐ahesthetized Rats |
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Anesthesiology,
Volume 73,
Issue 6,
1990,
Page 1198-1207
Hiroshi Nagasaka,
Tony Yaksh,
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摘要:
The effects of intrathecally administered adrenergic agonists (alpha-1-methoxamine, alpha-2-dexmedetomidine, clonidine, and ST-91, beta-isoproterenol) on nociceptive (tail-flick reflex) and cardiovascular changes (blood pressure and heart rate) evoked by immersing the tail in 53° C water were examined in rats anesthetized with halothane (0.75%) and in which intrathecal catheters had been chronically implanted. Administration of intrathecal alpha-2, but not alpha-1 or beta agonists, produced a dose-dependent block of the tail-flick and evoked cardiovascular responses with the order of activity being as follows: dexmedetomidine > clonidine > ST-91 >> methoxamine ≥ isoproterenol. These effects were readily reversed by the alpha-2 antagonist idazoxan. Intravenously administered dexmedetomidine at a dose that is active when given intratbecally (0.33 Mg) was without effect on either the tall-flick or the evoked cardiovascular responses. Without drugs, the halothane MAC was 1.23 ± 0.07%. In the presence of intrathecally administered dexmedetomidine (0.33 μg), the MAC was significantly reduced to 0.9 ± 0.09%. The intrathecal administration of alpha-2 agonists resulted in a rapid decrease in resting blood pressure and heart rate with the magnitude of hypotension being as follows: dexmedetomidine > clonidine > ST-91. These data suggest a potent spinal alpha-2-receptor-mediated modulation of somatomotor and autonomic responses to pain.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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19. |
Covalent Binding of Oxidative Biotransformation Intermediates Is Associated with Halothane Hepatotoxicity in Guinea Pigs |
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Anesthesiology,
Volume 73,
Issue 6,
1990,
Page 1208-1213
Richard Lind,
A Gandolfi,
Pauline de la M. Hall,
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摘要:
In vivocovalent binding of halothane biotransformation-reactive intermediates to hepatic protein and lipid was examined in association with the subsequent development of hepatic necrosis in the guinea pig. Oxidative halothane biotransformation was inhibited by the use of deuterated halothane, whereas reductive metabolism was enhanced by low inspired oxygen concentrations. Male outbred Hartley guinea pigs (n = 8) were exposed to either 1% (v/v) halothane or deuterated hatothane—with a fractional inspired O2concentration (FIo2) of 0.40 or 0.10—for 4 h. Livers removed from half of the animals immediately after anesthesia were evaluated for organic fluorine bound to protein and lipid. The remaining animals were evaluated for a hepatotoxic response up to 96 h after exposure. Only guinea pigs that received 1% halothane at an FIo2of 0.40 had centrilobular necrosis develop with significantly increased plasma alanine aminotransferase activities. All other treatment conditions significantly reduced oxidative halothane biotransformation, as indicated by decreased plasma trifluoroacetic add concentrations. These reductions were associated with a significant decrease in organic fluorine bound to hepatic proteins. An FIo2of 0.10 during halothane anesthesia significantly enhanced reductive biotransformation, as indicated by plasma fluoride ion concentrations. This was associated with a significant increase in organic fluoride bound to hepatic lipids. Centriobular necrosis did not develop under these conditions. Thus, covatent binding to subcellular proteins by the trifluoroacetyl add chloride intermediate generated by oxidative halothane biotransformation is implicated as a mechanism of centrilobular necrosis in guinea pigs. Binding to lipids by reductive pathway generated free radicals does not appear to be involved in production of the lesion.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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20. |
Morphine and Alfentanil Permeability Through the Spinal Dura, Arachnoid, and Pia Mater of Dogs and Monkeys |
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Anesthesiology,
Volume 73,
Issue 6,
1990,
Page 1214-1219
Christopher Bernards,
Harlan Hill,
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摘要:
Little information exists about which spinal meninx is the principal permeability barrier between the epidural space and the spinal cord or about what physiochemical properties of drug molecules govern their meningeal permeability. To better understand these aspects of epidural pharmacokinetics, the authors measured the permeability of morphine and alfentanil through the different components of the spinal meninges—dura mater, arachnoid mater, and pia mater—of dogs and monkeysin vitro.Live meningeal tissue from either species (dura mater alone, pia mater alone, or intact dura-arachnoid-pia) was placed between two fluid reservoirs of a temperature-controlled diffusion cell. The permeability of the tissues to each opioid was determined by placing the opioid in one of the reservoirs of the diffusion cell and measuring the rate at which the drug diffused through the tissue and appeared in the second reservoir. The arachnoid mater was found to be the major meningeal diffusion barrier between the epidural space and the spinal cord. Alfentanil was 3.7 times more permeable than morphine through all three meninges, suggesting that increased lipid solubility increases meningeal permeability. However, neither lipid solubility nor molecular weight adequately explained the difference in permeability between morphine and alfentanil. The authors conclude that thisin vitromodel has significant utility for studies aimed at predictingin vivomeningeal permeability and hence the potency and rapidity of action of any opioid administered by the epidural route.
ISSN:0003-3022
出版商:OVID
年代:1990
数据来源: OVID
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