bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Vasomotor Effects of Isoflurane in Subepicardial Resistance Vessels from Collateral-dependent and Normal Coronary Circulation of Pigs
Authors: Park Kyung W. , Lowenstein Edward , Dai Hai B. , Lopez John J. , Stamler Alon , Simons Michael , Sellke Frank W.
Published: November 2003

Background

The purpose of the current investigation was to determine and compare the direct effect of isoflurane on normal resistance coronary arteries and similarly sized coronary arteries in collateral-dependent (CD) circulation. A differential vasomotor effect of isoflurane might contribute to flow redistribution, either adverse or favorable, between normal and CD regions.

Methods

The authors used a swine model of chronic coronary occlusion. Six weeks after ameroid occluder placement around the left circumflex artery, the heart was removed. Myocardial blood flow, measured in vivo before the removal, was lower during rapid atrial pacing in the CD region than in the normally perfused region. These in vivo studies established the existence and location of CD circulation. Subepicardial microvessels, measuring approximately 100 microns, were dissected from both the CD region and the normal region. Either with or without preconstriction of the vessels with the thromboxane analogue U46619 1 microM, direct vasomotor effect of isoflurane was examined in vitro by video microscopy. In addition, vasomotor responses to endothelin-1, the endothelium-dependent dilator adenosine 5' diphosphate, and the endothelium-independent dilator sodium nitroprusside were compared between CD and normal resistance vessels.

Results

Isoflurane caused greater concentration-dependent constriction of the normal vessels than of the CD vessels (P < 0.05); this constrictive effect was masked by preconstriction of the vessels. Vasodilation of ADP was less in CD vessels than in normal vessels (P < 0.001), but vasodilation to sodium nitroprusside was not significantly different (P = 0.45). Vasoconstriction to endothelin-1 was greater in CD vessels than in normal vessels (P < 0.01).

Conclusions

The vasoconstrictive effect of isoflurane normally observed in coronary resistance vessels is impaired in resistance vessels that supply a CD area. The basis of this may be related to endothelial dysfunction.
Pulmonary Vascular Effects of Isoflurane Anesthesia after Left Lung Autotransplantation in Chronically Instrumented Dogs
Authors: Lennon Paul F. , Murray Paul A.
Published: November 2003

Background

Single lung transplantation has become a viable therapy for treatment of end-stage pulmonary disease. We previously observed that left lung autotransplantation (LLA) results in a chronic increase in pulmonary vascular resistance and enhanced pulmonary vascular reactivity to sympathetic alpha adrenoreceptor activation. The effects of inhalational anesthetics on the pulmonary circulation after lung transplantation have not been investigated. In the current study, the authors tested the hypothesis that isoflurane anesthesia, known to cause systemic vasodilation, would exert a vasodilator influence on the baseline pulmonary circulation after LLA. In addition, they tested the hypothesis that isoflurane anesthesia, known to attenuate the systemic vasoconstrictor response to sympathetic alpha adrenoreceptor agonists, would reduce the magnitude of the pulmonary vasoconstrictor response to sympathetic alpha adrenoreceptor activation after LLA.

Methods

Left pulmonary vascular pressure-flow (LPQ) plots were generated in chronically instrumented dogs by measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during inflation of a hydraulic occluder implanted around the right main pulmonary artery. Left pulmonary vascular pressure-flow plots were generated in 8 dogs 2-5 weeks after LLA in the conscious and isoflurane-anesthetized states at baseline, after beta adrenoreceptor block with propranolol, and during the cumulative administration of the alpha agonist, phenylephrine. Left pulmonary vascular pressure-flow plots also were generated in eight conscious, sham-operated control dogs at baseline, after beta block, and during phenylephrine administration.

Results

Compared with conscious control dogs, LLA resulted in a leftward shift (P < 0.01) in the baseline left pulmonary vascular pressure-flow relation, indicating chronic pulmonary vasoconstriction. Despite the enhanced level of pulmonary vasomotor tone after LLA, isoflurane did not exert a vasodilator influence on the baseline left pulmonary vascular pressure-flow relation. The pulmonary vasoconstrictor response to phenylephrine was enhanced (P < 0.01) after LLA compared with the response measured in conscious control dogs. The magnitude of the pulmonary vasoconstrictor response to phenylephrine after LLA was not attenuated during isoflurane anesthesia.

Conclusions

Isoflurane anesthesia does not exert a vasodilator influence on the pulmonary circulation in the setting of increased pulmonary vascular resistance after LLA. In addition, in contrast to previous studies of the systemic circulation, isoflurane does not attenuate the enhanced pulmonary vasoconstrictor response to sympathetic alpha adrenoreceptor activation after LLA.
Effects of Fetal pH on Local Anesthetic Transfer across the Human Placenta
Authors: Johnson Raymond F. , Herman Norman L. , Johnson H. Vernetta , Arney Timothy L. , Paschall Ray L. , Downing John W.
Published: November 2003

Background

Fetal acidemia increases umbilical venous bupivacaine concentrations in the in situ rabbit model. The authors studied the effects of decreasing fetal pH on the rate of maternal to fetal (M-->F) clearances of lidocaine, bupivacaine, 2-chloroprocaine, and antipyrine (a nonionic marker of placental transfer) across the isolated, dual perfused, human placental cotyledon.

Methods

Maternal to fetal clearances of bupivacaine, lidocaine, 2-chloroprocaine, and antipyrine were determined at fetal pH (7.4), during progressive fetal acidemia (pH 7.2-->7.0-->6.8), and after recovery to fetal pH 7.4 in experiments with both low protein state and in those with in vivo maternal and fetal protein-binding potentials.

Results

Placental transfer of all three agents increased linearly as the fetal pH decreased. Antipyrine transfer was unaffected. Clearance of lidocaine and bupivacaine, but not 2-chloroprocaine, returned to baseline when fetal pH was restored to 7.4. When maternal and fetal protein-binding potentials were increased, clearance at fetal pH 7.4 of bupivacaine, but not lidocaine, decreased significantly. During fetal acidemia, the transfer of both agents increased, but to a lesser extent than in the low protein concentration experiments.

Conclusions

Increasing the pH difference between maternal and fetal perfusates promotes M-->F passage of unionized lidocaine, bupivacaine, and 2-chloroprocaine. This likely results from an increased proportion of ionized local anesthetic in the acidemic fetal perfusate and consequent widening of the M-->F concentration gradient of the unionized form. Transfer of lidocaine and bupivacaine was limited by the maternal protein binding.
Direct Inhibitory Effect of Chlorpromazine on Smooth Muscle of the Porcine Pulmonary Artery
Authors: Sakihara Chie , Nishimura Junji , Kobayashi Sei , Takahashi Shosuke , Kanaide Hideo
Published: November 2003

Background

Chlorpromazine has been widely used by anesthesiologists to take advantage of its anesthesia-potentiating and vasorelaxing actions. However, the mechanisms of vasorelaxation induced by chlorpromazine are still not fully understood.

Methods

Using front-surface fluorometry of fura-2 and porcine pulmonary arterial strips, we investigated the effects of chlorpromazine on the intracellular Ca2+ concentration ([Ca2+]i) and force of vascular smooth muscle. The affinities of chlorpromazine and other neuroleptics to vascular alpha(1)-adrenergic receptors were then determined by a radio-ligand binding study.

Results

Chlorpromazine (as much as 1 microM) inhibited both the elevation of [Ca2+]i and force in pulmonary arterial smooth muscle induced by 80 mM K+-depolarization and 1 microM norepinephrine in a concentration-dependent manner. The extent of inhibition by chlorpromazine in norepinephrine-induced contraction was much greater than that in 80 mM K+-induced contraction. In contrast, as much as 1 microM chlorpromazine had no effect on the increases in [Ca2+]i or force induced by U46619, a thromboxane A2 analogue. Chlorpromazine also had no effect on the intracellular Ca2+ release induced by U46619. In a radio-ligand displacement study, chlorpromazine, haloperidol, phentolamine, trifluoperazine, and imipramine inhibited the specific binding of [3H]prazosin to the porcine aortic membranes, in this order of potency.

Conclusions

Chlorpromazine induces vasorelaxation through an alpha-adrenergic blocking action as well as a calcium antagonistic action; the former action may, therefore, play a major role in chlorpromazine-induced vasorelaxation.
Liposomal Bupivacaine
Authors: Mowat Jeffrey J. , Mok Miranda J. , MacLeod Bernard A. , Madden Thomas D.
Published: November 2003

Background

There is a clinical requirement for longer-acting local anesthetics, particularly for the management of post-operative and chronic pain. In this regard, liposomes have been suggested to represent a potentially useful vehicle for sustained drug release after local administration. In the current study, the authors used a transmembrane pH gradient to efficiently encapsulate bupivacaine within large unilamellar vesicles. They report on the kinetics of drug uptake and release and the duration of nerve blockade.

Methods

The rate and extent of bupivacaine uptake into large unilamellar vesicles that exhibit a pH gradient (interior acidic) were determined and compared to drug association with control liposomes that did not exhibit a proton gradient. In subsequent studies, researchers examined the kinetics of bupivacaine release from these liposome systems in vitro. Using the guinea pig cutaneous wheal model, the rate of clearance of the liposome carrier was monitored after intradermal administration, using a radiolabelled lipid marker, and the duration of nerve blockade produced by free and liposomal bupivacaine was compared.

Results

Bupivacaine was rapidly and efficiently accumulated within liposomes that exhibited a pH gradient (interior acidic) with trapping efficiencies of 64-82% of total drug, depending on the initial bupivacaine:phospholipid ratio. Little uptake was seen, however, for control vesicles that did not exhibit a transmembrane proton gradient. Using an in vitro model of drug clearance, liposomally encapsulated bupivacaine was found to be slowly released for a longer period of time compared with either the free drug or bupivacaine associated with control (no pH gradient liposomes). In the guinea pig cutaneous wheal model, more than 85% of the liposomal carrier was found to remain at the site of administration for 2 days. The sustained drug release afforded by liposomes that exhibited a pH gradient resulted in an increase in the duration of nerve blockade of as much as threefold compared with either the free drug or bupivacaine in the presence of control (no pH gradient) liposomes. Recovery of half maximal response (R2.5) after administration of 0.75% free bupivacaine, for example, was approximately 2 h, whereas the same dose of bupivacaine in pH gradient liposomes exhibited a R2.5 of approximately 6.5 h.

Conclusions

Large unilamellar vesicles that exhibit a pH gradient can efficiently encapsulate bupivacaine and subsequently provide a sustained-release system that greatly increases the duration of neural blockade.
Small, Oral Dose of Clonidine Reduces the Incidence of Intraoperative Myocardial Ischemia in Patients Having Vascular Surgery
Authors: Stuhmeier Klaus-Dieter , Mainzer Bernd , Cierpka Jochen , Sandmann Wilhelm , Tarnow Jorg
Published: November 2003

Background

Most new perioperative myocardial ischemic episodes occur in the absence of hypertension or tachycardia. The ability of alpha 2-adrenoceptor agonists to inhibit central sympathetic outflow may benefit patients with coronary artery disease by increasing the myocardial oxygen supply and -demand ratio.

Methods

A randomized double-blind study design was used in 297 patients scheduled to have elective vascular surgical procedures to evaluate the effects of 2 micrograms/kg-1 oral clonidine (n = 145) or placebo (n = 152) on the incidence of perioperative myocardial ischemic episodes, myocardial infarction, and cardiac death. Continuous real-time S-T segment trend analysis (lead II and V5) was performed during anesthesia and surgery and correlated with arterial blood pressure and heart rate before and during ischemic events. Dose requirements for vasoactive and antiischemic drugs to control blood pressure and heart rate as well as episodes of myocardial ischemia (i.e., catecholamines, beta-adrenoceptor antagonists, nitrates, and systemic vasodilators) and fluid volume load were recorded.

Results

Administration of clonidine reduced the incidence of perioperative myocardial ischemic episodes from 39% (59 of 152) to 24% (35 of 145) (P < 0.01). Hemodynamic patterns, percentage of ischemic time, and the number of ischemic episodes per patient did not differ. Nonfatal myocardial infarction developed after operation in four patients receiving placebo compared with none receiving clonidine (day 2 to 21; P = 0.07). The incidence of fatal cardiac events (1 vs. 2) was not different. Dose requirements for vasoactive and antiischemic drugs did not differ between the groups, but the amount of presurgical fluid volume was slightly greater in patients receiving clonidine (951 +/- 388 vs. 867 +/- 381 ml; P < 0.03).

Conclusion

A small oral dose of clonidine, given prophylactically, can reduce the incidence of perioperative myocardial ischemic episodes without affecting hemodynamic stability in patients with suspected or documented coronary artery disease.
Effect of Flumazenil on Ventilatory Drive during Sedation with Midazolam and Alfentanil
Authors: Gross Jeffrey B. , Blouin Robert T. , Zandsberg Shaul , Conard Pattilyn F. , Haussler Jurgen
Published: November 2003

Background

Patients who receive a combination of a benzodiazepine and an opioid for conscious sedation are at risk for developing respiratory depression. While flumazenil effectively antagonizes the respiratory depression associated with a benzodiazepine alone, its efficacy in the presence of both a benzodiazepine and an opioid has not been established. This study was designed to determine whether flumazenil can reverse benzodiazepine-induced depression of ventilatory drive in the presence of an opioid.

Methods

Twelve healthy volunteers completed this randomized, double-blind, crossover study. Ventilatory responses to carbon dioxide and to isocapnic hypoxia were determined during four treatment phases: (1) baseline, (2) alfentanil infusion; (3) combined midazolam and alfentanil infusions, and (4) combined alfentanil, midazolam, and "study drug" (consisting of either flumazenil or flumazenil vehicle) infusions. Subjects returned 2-6 weeks later to receive the alternate study drug.

Results

Alfentanil decreased the slope of the carbon dioxide response curve from 2.14 +/- 0.40 to 1.43 +/- 0.19 l.min-1.mmHg-1 (x +/- SE, P < 0.05), and decreased the minute ventilation at P(ET)CO2 = 50 mmHg (VE50) from 19.7 +/- 1.2 to 14.8 +/- 0.9l.min-1 (P < 0.05). Midazolam further reduced these variables to 0.87 +/- 0.17 l.min-1.mmHg-1 (P < 0.05) and 11.7 +/- 0.8 l.min-1 (P < 0.05), respectively. With addition of flumazenil, slope and VE50 increased to 1.47 +/- 0.37 l.min-1.mmHg-1 (P < 0.05) and 16.4 +/- 2.0l.min-1 (P < 0.05); after placebo, the respective values of 1.02 +/- 0.19 l.min-1.mmHg-1 and 12.5 +/- 1.2 l.min-1 did not differe significantly from their values during combined alfentanil and midazolam administration. The effect of flumazenil differed significantly from that of placebo (P < 0.05). Both the slope and the displacement of the hypoxic ventilatory response, measured at P(ET)CO2 = 46 +/- 1 mmHG, were affected similarly, with flumazenil showing a significant improvement compared to placebo.

Conclusions

Flumazenil effectively reverses the benzodiazepine component of ventilatory depression during combined administration of a benzodiazepine and an opioid.
Human Chest Wall Function during Epidural Anesthesia
Authors: Warner David O. , Warner Mark A. , Ritman Erik L.
Published: November 2003

Background

Although epidural anesthesia (EA) can significantly disrupt the function of the respiratory system, data concerning its effects on respiratory muscle activity and the resulting motion of the chest wall are scarce. This study aimed to determine the effects of lumbar EA on human chest wall function during quiet breathing.

Methods

Six persons were studied while awake and during mid-thoracic (approximately a T6 sensory level) and high (approximately a T1 sensory level) lumbar EA produced by either 2% lidocaine (two persons) or 1.5% etidocaine (four persons) with 1:200,000 epinephrine. Respiratory muscle activity was measured using fine-wire electromyography electrodes. Chest wall configuration during high EA was determined using images of the thorax obtained by three-dimensional, fast computed tomography. The functional residual capacity was measured using a nitrogen dilution technique.

Results

High EA abolished activity in the parasternal intercostal muscles of every participant but one, whereas the mean phasic activity of the scalene muscles was unchanged. High EA significantly decreased the inspiratory volume displacement of the rib cage compared with intact breathing but did not have a significant effect on diaphragm displacement. Therefore, high EA decreased the percentage contribution of rib cage expansion to inspiratory increases in thoracic volume (delta Vth) (from 27 +/- 2 [MSE] to 10 +/- 11% of delta Vth). Paradoxic rib cage motion during inspiration (i.e., a net inward motion during inspiration) developed in only one participant. High EA substantially increased the functional residual capacity (by 295 +/- 89 ml), with a significant net caudad motion of the end expiratory position of the diaphragm. In addition, high EA significantly decreased the volume of liquid in the thorax at end expiration in five of the six participants, a factor that also contributed to the increase in functional residual capacity in these persons.

Conclusions

Rib cage expansion continues to contribute to tidal volume during high EA in most subjects, even when most of the muscles of the rib cage are paralyzed; the mean phasic electrical activity of unblocked respiratory muscles such as scalenes does not increase in response to rib cage muscle paralysis produced by EA; and high EA increases the functional residual capacity, an increase produced in most participants by a caudad motion of the diaphragm and a decrease in intrathoracic blood volume.
Minimum Alveolar Concentration of Halothane and Enflurane Are Decreased in Early Pregnancy
Authors: Chan Matthew T.V. , Mainland Phoebe , Gin Tony
Published: November 2003

Background

Minimum alveolar concentration (MAC) of isoflurane is decreased in early pregnancy but it is not known whether this occurs to the same extent with other inhalational anesthetics. The MAC of halothane and enflurane were compared in pregnant women undergoing elective termination of pregnancy and in nonpregnant women.

Methods

We studied 16 pregnant women scheduled for termination of pregnancy at 8 to 13 weeks gestation and 16 non-pregnant patients undergoing laparoscopic sterilization. Eight patients in each group received halothane and the others received enflurane. After inhalational induction of anesthesia and tracheal intubation, MAC was determined in each patient by observing the motor response to a 10-s, 50-Hz, 80-mA transcutaneous electric tetanic stimulus to the ulnar nerve at varying concentrations of either halothane or enflurane. The end-tidal concentration of inhalational anesthetic was kept constant for at least 15 min before each stimulus and the concentration was varied ultimately in steps of 0.05 vol% (halothane) or 0.10 vol% (enflurane) until a sequence of three alternate responses (move, not move, move) or (not move, move, not move) was obtained. Minimum alveolar concentration for each person was taken as the mean of the two concentrations just permitting and just preventing movement, and MAC for the group was the median of individual MAC values. Confidence intervals were calculated for the percentage decrease in MAC for pregnant women compared with nonpregnant women.

Results

The median (range) MAC of halothane, 0.58 vol% (0.53 to 0.58), and enflurane, 1.15 vol% (0.95-1.25), in the pregnant women were less than those in the nonpregnant women, 0.75 vol% (0.70 to 0.78), P = 0.0005 and 1.65 vol% (1.45 to 1.75), P = 0.0007, respectively. The percentage decrease (95% CI) in MAC for pregnant women was 27% (20 to 27%) for halothane and 30% (24 to 36%) for enflurane.

Conclusions

The MAC of halothane and enflurane were reduced by a similar degree in pregnant women at 8 to 13 weeks gestation compared with nonpregnant women.
Effects of General Anesthesia and Paralysis on Upper Airway Changes Due to Head Position in Humans
Authors: Sivarajan Murali , Joy James V.
Published: November 2003

Background

In supine patients with their heads in flexion, general anesthesia causes posterior displacement of upper airway structures that is associated with airway obstruction, and extension of the head helps restore patency. However, the independent effects of head position, general anesthesia, and muscle paralysis on upper airway structures are not known.

Methods

Lateral radiographs of the neck were taken in supine patients with the head in flexion and extension, during consciousness, and after induction of general anesthesia and muscle paralysis. The following measurements were made distances from the horizontal plane to the epiglottis, the hyold, and the thyroid cartilage to detect anteroposterior displacements; distances from the transverse plane to the hyold and the thyroid cartilage to detect cephalocaudad displacements; and widths of the oropharynx, the laryngeal vestibule, and the laryngeal sinus.

Results

With the head in flexion, anesthesia and paralysis compared with the conscious state caused posterior displacement of the epiglottis, narrowing of the oropharynx, and widening of the laryngeal vestibule. With the head in extension, anesthesia and paralysis compared with the conscious state caused anterior displacements of the epiglottis, the hyold, and the thyroid cartilage, narrowing of the oropharynx, and widening of the laryngeal vestibule and the laryngeal sinus.

Conclusion

Loss of tonic muscular activity due to anesthesia and paralysis results in anteroposterior displacements of the upper airway structures with flexion and extension of the head that are in the same direction as that of the mandible. Anesthesia and paralysis also widen the dimensions of the larynx. These changes might have implications for instrumentation and protection of the airway during general anesthesia or unconsciousness.
Peripheral and Spinal Actions of Opioids in the Blockade of the Autonomic Response Evoked by Compression of the Inflamed Knee Joint
Authors: Nagasaka Hiroshi , Awad Hamdy , Yaksh Tony L.
Published: November 2003

Background

Three types of opioid receptors, mu, delta, and kappa, are present in the periphery and in the central nervous system. In contrast to the effects in the central nervous system, the antinociceptive action of opioids in the periphery is not as well characterized. The effects of intraarticular, spinal, and intramuscular injections of mu, delta, and kappa opioid agonists on the autonomic response evoked by compression of an inflamed knee joint were evaluated.

Methods

In halothane-anesthetized rats, arthritis was induced by injecting kaolin and carrageenan into the right knee joint. Standardized compression of the knee joint by inflation of a pediatric blood pressure cuff to 200 mmHg for 2 min produced a reliable stimulus-dependent hypertension (delta = 13 mmHg). Drugs were delivered intramuscularly, intrathecally through a chronic catheter, or intraarticularly into the right knee joint. The drug injection was performed 4 hr after induction of the inflammation.

Results

The intrathecal administration of mu, delta, and kappa agonists resulted in a dose-dependent blockade of the cuff-evoked increase in blood pressure. The order of intrathecal drug activity on the compression-evoked blood pressure responses with median effective dose (ED50) was sufentanil (0.02 nmol; mu) > PD117302 (0.5 nmol; kappa); spiradoline (1.5 nmol; kappa) morphine (2.4 nmol; mu) > DADL (15 nmol; delta); DPDPE (18 nmol; delta) > U-50,488H (620 nmol; kappa) > naloxone = 0. The intraarticular administration of mu and kappa, but not delta agonists, produced a dose-dependent blockade of a compression-evoked increase in blood pressure, with the order of drug activity (ED40) as follows: sufentanil (0.04 mumol) > PD117302 (0.3 mumol); spiradoline (0.8 mumol), morphine (0.9 mumol) > U-50,488H (0.9 mumol) > DPDPE (> 5 mumol); DADL (> 18 mumol) > naloxone = 0. Intramuscular injection of these agonists caused suppression, with the order of drug activity (ED50) as follows: sufentanil (0.2 mumol) > PD117302 (2 mumol); spiradoline (11 mumol) morphine (9 mumol) > DPDPE (> 5 mumol); DADL (18 mumol) > U-50,488H (22 mumol) > naloxone = 0. All intraarticular effects were reversible by injecting naloxone intramuscularly, with the ordering of naloxone potency against equiactive doses of morphine > U50,488H.

Conclusions

The activity of the respective agonists and the intraarticular > intramuscular ordering of systemic potency in this model indicate that opioids, by an action at mu and kappa, can exert a direct antihyperalgesic action at the terminals of primary afferents projecting to a region of inflammation. These observations offer strong support for a peripheral action of opioids in certain states in inflammation-induced hyperalgesia.
Volatile Anesthetics Depress Glutamate Transmission Via Presynaptic Actions
Authors: MacIver Bruce M. , Mikulec Anthony A. , Amagasu Shanti M. , Monroe Frances A.
Published: November 2003

Background

Recent evidence for a presynaptic depression of glutamate release produced by volatile anesthetics prompted the current study of isoflurane and halothane effects on glutamate-mediated transmission in the mammalian central nervous system.

Methods

Electrophysiologic recordings from CA1 neurons in rat hippocampal brain slices were used to measure anesthetic effects on glutamate-mediated excitatory postsynaptic potential (EPSP) amplitudes and paired pulse facilitation. Paired pulse facilitation is known to be altered when the calcium-dependent release of glutamate is depressed, but not when EPSP amplitudes are depressed by postsynaptic mechanisms.

Results

Isoflurane depressed EPSP amplitudes over a concentration range of 0.35-2.8 vol %, with a 50% depression (EC50) occurring at 1.0 vol % (0.71 rat minimum alveolar concentration). This depression was accompanied by an increase in paired-pulse facilitation of approximately 30% at 1.7 vol %, using interpulse intervals of 120 ms. Halothane depressed EPSP amplitudes in a concentration-dependent manner (0.3-2.4 vol %, EC50 = 1.1 minimum alveolar concentration; 1.3 vol %) and also increased facilitation by approximately 20% at 1.2 vol %. These effects persisted in the presence of 10 microM bicuculline, indicating that enhanced gamma-aminobutyric acid-mediated inhibition was not involved. The anesthetic-induced increase in facilitation and EPSP depression was mimicked by lowering extracellular calcium, which is known to depress glutamate release at these synapses. The postsynaptic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione depressed EPSP amplitudes with no change in facilitation.

Conclusions

Our results confirm earlier findings that clinically relevant concentrations of volatile anesthetics depress glutamate-mediated synaptic transmission. The observed increases in synaptic facilitation support recent findings from biochemical and electrophysiologic studies indicating presynaptic sites of action contribute to anesthetic-induced depression of excitatory transmission. This anesthetic-induced reduction in glutamate release would contribute to the central nervous system depression associated with anesthesia by adding to postsynaptic depressant actions on glutamate receptors.
Antinociceptive Response to Nitrous Oxide Is Mediated by Supraspinal Opiate and Spinal α2Adrenergic Receptors in the Rat
Authors: Guo Tian-Zhi , Poree Lawrence , Golden Wendy , Stein Joshua , Fujinaga Masahiko , Maze Mervyn
Published: November 2003

Background

Despite nearly 150 years of clinical use, the mechanism(s) of action of nitrous oxide (N2O) remains in doubt. In some but not all studies the analgesic properties of N2O can be attenuated by opiate receptor antagonists. The purported mechanism for the opiate antagonistic effect relates to the finding that N2O increases supraspinal levels of endogenous opiates, although this finding has been disputed. Based on the observations that (1) N2O promotes the release of catecholamines, including the endogenous alpha 2 adrenergic agonist norepinephrine, and (2) that descending noradrenergic inhibitory pathways are activated by opioid analgesics, this study sought to determine whether alpha 2 adrenergic receptors are involved in the antinociceptive action of nitrous oxide.

Methods

Institutional approval was obtained for the study. Rats breathed 70% N2O and 30% O2 in an enclosed chamber. After a 30-min exposure, significant antinociception was indicated by an increase in the latency response to a noxious stimulus (tail-flick latency). The tail-flick latency was tested in rats exposed to 70% N2O after either systemic or regional (intrathecal or intracerebroventricular) injections with either competitive (atipamezole; yohimbine) or noncompetitive (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) alpha 2 adrenoceptor antagonists, or the opiate receptor antagonist naloxone.

Results

When administered systemically, both the opiate (naloxone) and alpha 2 adrenoceptor antagonists (atipamezole, yohimbine, and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) blocked the enhanced tail-flick latency response to N2O-Naloxone administered intracerebroventricularly, but not intrathecally, blocked the enhanced tail-flick latency response to N2O. Conversely, atipamezole administered intrathecally, but not intracerebroventricularly, blocked the enhanced tail-flick latency response to N2O.

Conclusions

These data suggest that both supraspinal opiate and spinal alpha 2 adrenoceptors play a mediating role in the antinociceptive response to N2O in rats. A possible mechanism may involve a descending inhibitory noradrenergic pathway that may be activated by opiate receptors in the periaqueductal gray region of the brain stem in the rat after exposure to N2O.
Prevention of Lidocaine Aerosol-induced Bronchoconstriction with Intravenous Lidocaine
Authors: Bulut Yonca , Hirshman Carol A. , Brown Robert H.
Published: November 2003

Background

Lidocaine applied topically provokes bronchoconstriction in persons with hyperreactive airway disease. The authors questioned whether intravenous lidocaine would prevent lidocaine-aerosol induced bronchoconstriction. They compared the effects of lidocaine administered intravenously and by the aerosol route on baseline airway tone, and on the prevention of histamine-induced bronchoconstriction in five Basenji-Greyhound dogs.

Methods

Dogs were pretreated with either intravenous or aerosol lidocaine followed by histamine aerosol challenge. On separate days, dogs were pretreated with intravenous lidocaine, followed by aerosol lidocaine administration at similar doses. Airway caliber was assessed using high-resolution computed tomography. Data were analyzed by two-way analysis of variance. Serum lidocaine concentrations were obtained.

Results

Histamine alone decreased the airway area by 32 +/- 3%. Lidocaine administered intravenously or by the aerosol route significantly inhibited histamine-induced bronchoconstriction. There was no significant difference between the two routes in preventing histamine-induced bronchoconstriction. At the dose that inhibited histamine-induced bronchoconstriction, lidocaine administered by the aerosol route decreased baseline airway area by 27 +/- 3% (P < 0.01), whereas intravenous lidocaine had no effect. Intravenous lidocaine prevented lidocaine aerosol-induced bronchoconstriction, and the combination of intravenous and aerosol lidocaine significantly dilated the airways by 20 +/- 5% (P < 0.01 compared with control).

Conclusions

An intravenous bolus of lidocaine prevents the initial bronchoconstriction induced by lidocaine when administered as an aerosol.
High-volume, Zero-balanced Hemofiltration to Reduce Delayed Inflammatory Response to Cardiopulmonary Bypass in Children
Authors: Journois Didier , Israel-Biet Dominique , Pouard Philippe , Rolland Benedicte , Silvester William , Vouhe Pascal , Safran Denis
Published: November 2003

Background

In previous studies, researchers suggested a beneficial role of hemofiltration performed during cardiopulmonary bypass in children. This study was performed to assess both clinical effects and inflammatory mediator removal by high-volume, zero-fluid balance ultrafiltration during rewarming (Z-BUF).

Methods

Twenty children undergoing cardiac surgery were assigned randomly to Z-BUF or a control group. Plasma C3a, interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor, myeloperoxidase, and leukocyte count were measured before (T1) and after (T2) hemofiltration and 24 h later (T3). The intensive care unit staff was blinded to the patient's group. Postoperative alveolar-arterial oxygen gradient, time to extubation, body temperature, and postoperative blood loss were monitored.

Results

Ultrafiltration rate was 4,972 (3,183-6,218) mL/m2 (median [minimum-maximum]) in the Z-BUF group, where significant reductions were observed in postoperative blood loss, time to extubation (10.8[9-18] vs. 28.2 [15-58] h) and postoperative alveolar-arterial oxygen gradient (320 [180-418] vs. 551 [485-611] mmHg at T3). In the Z-BUF group, significant removal of tumor necrosis factor, IL-10, myeloperoxidase, and C3a were observed at T2. Interleukin 1, IL-6, IL-8, and myeloperoxidase were decreased at T3, suggesting earlier removal of factor(s) that may trigger their release.

Conclusions

These results suggest that hemofiltration exerts some beneficial clinical effects that are not due to water removal. The role of the early removal of factors triggering the inflammatory response, rather than a direct removal of cytokines, deserves further investigation.
Detection of Intraoperative Incidents by Electronic Scanning of Computerized Anesthesia Records
Authors: Sanborn Kevin V. , Castro Jose , Kuroda Max , Thys Daniel M.
Published: November 2003

Background

The use of a computerized anesthesia information management system provides an opportunity to scan case records electronically for deviations from specific limits for physiologic variables. Anesthesia department policy may define such deviations as intraoperative incidents and may require anesthesiologists to report their occurrence. The actual incidence of such events is not known. Neither is the level of compliance with voluntary reporting.

Methods

Using automated anesthesia record-keeping with long-term storage, physiologic data were recorded every 15 s from 5,454 patients undergoing noncardiothoracic surgery. Recorded measurements of blood pressure, heart rate, arterial oxygen saturation, and temperature were electronically analyzed for deviations from defined limits. The computer system also was used by anesthesiologists to report voluntarily those deviations as intraoperative incidents. For each electronically detected incident: 1) the complete automated anesthesia record was examined by two senior anesthesiologists who, by consensus, eliminated case records with artifact or in which context suggested that the incident was not clinically relevant, and 2) the anesthesia information management system database was checked for voluntary reporting.

Results

In 473 automated anesthesia records, 494 incidents were found by electronic scanning of 5,454 automated anesthesia records. Sixty intraoperative incidents were eliminated, 25 due to artifact and 35 due to context. When the remaining 434 intraoperative incidents were checked for voluntary reporting, 18 (4.1%) matching voluntary reports were found. All intraoperative incidents that were reported voluntarily also were detected by electronic scanning. Based on a 10% sample, the sensitivity rate of electronic scanning was 97.2% (35/36), and the specificity rate was 98.4% (427/434). Among 413 cases with electronically detected intraoperative incidents, there were 29 deaths (7.0%), whereas there were only 79 deaths (1.6%) among 5,041 cases without incidents (chi 2 = 58.5, P < 0.001).

Conclusions

The use of an anesthesia information management system facilitated analysis of intraoperative physiologic data and identified certain intraoperative incidents with high sensitivity and specificity. A low level of compliance with voluntary reporting of defined intraoperative incidents was found for all anesthesiologists studied. Finally, there was a strong association between intraoperative incidents and in-hospital mortality.
Clinical and Bacteriologic Survey of Epidural Analgesia in Patients in the Intensive Care Unit
Authors: Darchy Bruno , Forceville Xavier , Bavoux Eric , Soriot Frederic , Domart Yves
Published: November 2003

Background

The risk of bacterial contamination related to epidural analgesia in patients cared for in the intensive care unit has not been assessed. Thus the authors studied patients who received care in the intensive care unit who were given epidural analgesia for more than 48 h to determine the rates of local, epidural catheter, and spinal space infection and to identify risk factors.

Methods

Each patient receiving epidural analgesia for longer than 48 h was examined daily for local and general signs of infection. A swab sample for culture was taken if there was local discharge; all epidural catheters were cultured on withdrawal. All patients underwent weekly neurologic monitoring for 1 month; those with positive epidural catheter cultures had one spinal magnetic resonance image scan.

Results

The 75 patients cared for in the intensive care unit who were studied had been receiving epidural analgesia for a median of 4 days (interquartile range, 3.5 to 5 days). Twenty-seven patients had signs of local inflammation (erythema or local discharge), and nine of these had infections. All the patients who had both local signs also had infection. All nine infections were local (12%), but four patients also had epidural catheter infections (5.3%). No patient with erythema alone or without local signs had a positive epidural catheter culture. No spinal space infection was diagnosed. Staphylococcus epidermidis was the most frequently cultured microorganism. Local infection was treated by removing the epidural catheter without any antibiotics. Concomitant infection at other sites (21 of 75 patients, or 28%), antibiotic therapy (64 of 75 patients, or 85%), the duration of epidural analgesia, and the insertion site level of the epidural catheter were not identified as risk factors for epidural analgesia-related infections.

Conclusions

The risk of epidural analgesia-related infection in patients in the intensive care unit seems to be low. The presence of two local signs of inflammation is a strong predictor of local and epidural catheter infection.
Immunoisolated Xenogeneic Chromaffin Cell Therapy for Chronic Pain
Authors: Buchser E. , Goddard M. , Heyd B. , Joseph J. M. , Favre J. , de Tribolet N. , Lysaght M. , Aebischer P.
Published: November 2003

Background

Chromaffin cells from the adrenal gland secrete a mixture of compounds that have a strong analgesic effect, especially when administered intrathecally. Many studies in animal models have shown that discordant xenogeneic cell isolates, including chromaffin cells, can survive and have biologic effects when transplanted within a semipermeable membrane capsule.

Methods

To evaluate the clinical potential of encapsulated cell therapy, a human-scale implant containing bovine chromaffin cells was developed, characterized, and implanted in the subarachnoid space of seven patients with severe chronic pain not satisfactorily managed with conventional therapies. Patients received no pharmacologic immunosuppression. Cell devices were implanted during minimally invasive surgery, and device design allowed retrieval. All devices were recovered after implant periods of 41 to 176 days.

Results

Postexplant histologic analysis, immunostaining, and secretory function all confirmed survival and biochemical function of the encapsulated cells. Reductions in morphine intake and improvement in pain ratings were observed in several patients.

Conclusions

This study represents the first successful trial of encapsulated xenogeneic cells in humans. The preliminary findings of pain reduction warrant the initiation of a randomized, double-blind phase II study to evaluate the potential efficacy of the procedure.
Double-blind, Randomized Comparison of Ondansetron and Intraoperative Propofol to Prevent Postoperative Nausea And Vomiting
Authors: Gan T. J. , Ginsberg B. , Grant A. P. , Glass P. S. A.
Published: November 2003

Background

Breast surgery is associated with a high incidence of postoperative nausea and vomiting. Propofol and prophylactic administration of ondansetron are associated with a lower incidence of postoperative nausea and vomiting. To date no comparison of these two drugs has been reported. A randomized study was done to compare the efficacy of ondansetron and intraoperative propofol given in various regimens.

Methods

Study participants included 89 women classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled for major breast surgery. Patients were randomly assigned to one of four groups. Group O received 4 mg ondansetron in 10 ml 0.9% saline and groups PI, PIP, and PP received 10 ml 0.9% saline before anesthesia induction. Group O received thiopental, isoflurane, nitrous oxide-oxygen, and fentanyl for anesthesia. Group PI received propofol, isoflurane, nitrous oxide-oxygen, and fentanyl. Group PIP received propofol, isoflurane, nitrous oxide-oxygen, and fentanyl. Thirty minutes before expected skin closure, isoflurane was discontinued and 50 to 150 micrograms.kg-1.min-1 propofol was given intravenously to maintain anesthesia. Group PP received propofol for induction and maintenance of anesthesia, nitrous oxide-oxygen, and fentanyl. Postoperative pain relief was provided with morphine administered by a patient-controlled analgesia pump. The incidence of nausea and vomiting, requests for rescue antiemetic and sedation, pain scores, and hemodynamic data were recorded for 24 h.

Results

Within 6 h of surgery, groups O and PP had a lower incidence of nausea compared with groups PI and PIP (P < 0.05). Fewer patients in group PP (19%) vomited during the 24-h period compared with groups O (48%), PI (64%), and PIP (52%) (P < 0.05). The incidence of antiemetic use was also less in group PP (P < 0.05). Patients in group PP had lower sedation scores at 30 min and at 1 h (P < 0.05). There were no differences among the groups in pain scores, blood pressure, heart rate, respiratory rate, and incidence of pruritus.

Conclusions

Propofol administered to induce and maintain anesthesia is more effective than ondansetron (with thiopental-isoflurane anesthesia) in preventing postoperative vomiting and is associated with fewer requests for rescue antiemetic and sedation in the early phase of recovery. It is equally effective in preventing postoperative nausea as ondansetron in the first 6 h after operation. Propofol used only as an induction agent or for induction and at the end of surgery were not as protective against postoperative nausea and vomiting.
Tranexamic Acid Reduces Blood Loss, Transfusion Requirements, and Coagulation Factor Use in Primary Orthotopic Liver Transplantation
Authors: Boylan John F. , Klinck John R. , Sandler Alan N. , Arellano Ramiro , Greig Paul D. , Nierenberg Hilary , Roger Sandra L. , Glynn Michael F. X.
Published: November 2003

Background

Patients with end-stage liver disease frequently incur large-volume blood loss during liver transplantation associated with mechanical factors, preexisting coagulopathy, and intraoperative fibrinolysis.

Methods

Between April 1992 and May 1994, the authors of this double-blind, randomized, placebo-controlled study examined the effect of high-dose tranexamic acid (maximum of 20 g) on blood loss and blood product requirements in patients undergoing primary isolated orthotopic liver transplantation. Primary outcome measures were volume of blood loss (intraoperative blood loss and postoperative drainage) and erythrocyte, plasma, platelet, and cryoprecipitate use during surgery and the first 24 h of intensive care unit stay.

Results

Patients receiving tranexamic acid (n = 25) had less intraoperative blood loss (median, 4.3 l; interquartile range, 2.5 to 7.9; P = 0.006) compared with the placebo group (n = 20; median, 8 l; interquartile range, 5 to 15.8), and reduced intraoperative plasma, platelet, and cryoprecipitate requirements. Median perioperative erythrocyte use was 9 units (interquantile range, 4 to 14 units) in patients receiving tranexamic acid and 13 units (interquantile range, 7.5 to 31 units) in controls (P = 0.03). Total perioperative donor exposure was 20.5 units (interquantile range, 16 to 41 units) in patients receiving tranexamic acid and 43.5 units (interquantile range, 29.5 to 79 units) in controls (P = 0.003). Results for postoperative wound drainage were similar. Hospital stay and need for retransplantation were comparable in both groups. No patient in either group showed clinical evidence of hepatic artery or portal venous thrombosis within 1 month of transplantation.

Conclusions

High-dose tranexamic acid significantly reduces intraoperative blood loss and perioperative donor exposure in patients with end-stage parenchymal liver disease who are undergoing orthotopic liver transplantation, with marked reductions in platelet and cryoprecipitate requirements.
Omission of Nitrous Oxide during Anesthesia Reduces the Incidence of Postoperative Nausea and Vomiting
Authors: Divatia Jigeeshu V. , Vaidya Jayant S. , Badwe Rajendra A. , Hawaldar Rohini W.
Published: November 2003

Background

Postoperative nausea and vomiting are important causes of morbidity after general anesthesia. Nitrous oxide has been implicated as an emetogenic agent in many studies. However, several other trials have failed to sustain this claim. The authors tried to resolve this issue through a meta-analysis of randomized controlled trials comparing the incidence of postoperative nausea and vomiting after anesthesia with or without nitrous oxide.

Methods

Of 37 published studies retrieved by a search of articles indexed on the MEDLINE database from 1966 to 1994, 24 studies (26 trials) with distinct nitrous-oxide and non-nitrous oxide groups were eligible for the meta-analysis. The pooled odds ratio and relative risk were calculated. Post boc subgroup analysis was also performed to qualify the result.

Results

The pooled odds ratio was 0.63 (0.53 to 0.75). Omission of nitrous oxide reduced the risk for postoperative nausea and vomiting by 28% (18% to 37%). In the subgroup analysis, the maximal effect of omission of nitrous oxide was seen in female patients. In patients undergoing abdominal surgery and general surgical procedures, the effect of omission of nitrous oxide, although in the same direction, was not significant.

Conclusion

Omission of nitrous oxide reduced the odds of postoperative nausea and vomiting by 37%, a reduction in risk of 28%.