bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural Mechanisms of Antinociceptive Effects of Hypnosis
Authors: Faymonville Marie Elisabeth , Laureys Steven , Degueldre Christian , DelFiore Guy , Luxen André , Franck Georges , Lamy Maurice , Maquet Pierre
Published: August 2004

Background

The neural mechanisms underlying the modulation of pain perception by hypnosis remain obscure. In this study, we used positron emission tomography in 11 healthy volunteers to identify the brain areas in which hypnosis modulates cerebral responses to a noxious stimulus.

Methods

The protocol used a factorial design with two factors: state (hypnotic state, resting state, mental imagery) and stimulation (warm non-noxious vs. hot noxious stimuli applied to right thenar eminence). Two cerebral blood flow scans were obtained with the 15O-water technique during each condition. After each scan, the subject was asked to rate pain sensation and unpleasantness. Statistical parametric mapping was used to determine the main effects of noxious stimulation and hypnotic state as well as state-by-stimulation interactions (i.e., brain areas that would be more or less activated in hypnosis than in control conditions, under noxious stimulation).

Results

Hypnosis decreased both pain sensation and the unpleasantness of noxious stimuli. Noxious stimulation caused an increase in regional cerebral blood flow in the thalamic nuclei and anterior cingulate and insular cortices. The hypnotic state induced a significant activation of a right-sided extrastriate area and the anterior cingulate cortex. The interaction analysis showed that the activity in the anterior (mid-)cingulate cortex was related to pain perception and unpleasantness differently in the hypnotic state than in control situations.

Conclusions

Both intensity and unpleasantness of the noxious stimuli are reduced during the hypnotic state. In addition, hypnotic modulation of pain is mediated by the anterior cingulate cortex.
Smoking Decreases Alveolar Macrophage Function during Anesthesia and Surgery
Authors: Kotani Naoki , Hashimoto Hiroshi , Sessler Daniel I. , Yoshida Hitoshi , Kimura Naomasa , Okawa Hirobumi , Muraoka Masatoshi , Matsuki Akitomo
Published: August 2004

Background

Smoking changes numerous alveolar macrophage functions and is one of the most important risk factors for postoperative pulmonary complications. The current study tested the hypothesis that smoking impairs antimicrobial and proinflammatory responses in alveolar macrophages during anesthesia and surgery.

Method

The authors studied 30 smoking and 30 nonsmoking patients during propofol-fentanyl general anesthesia. Alveolar immune cells were harvested by bronchoalveolar lavage immediately and 2, 4, and 6 h after induction of anesthesia and at the end of surgery. The types of alveolar immune cell and macrophage aggregation were determined. The authors measured opsonized and unopsonized phagocytosis. Microbicidal activity was determined as the ability of the macrophages to kill Listeriamonocytogenes directly. Finally, RNA was extracted from harvested cells and cDNA was synthesized by reverse transcription. The expression of interleukin 1beta, 6, and 8, interferon gamma, and tumor necrosis factor alpha were measured by semiquantitative polymerase chain reaction using beta-actin as an internal standard.

Results

The fraction of aggregated macrophages increased significantly over time in both groups, whereas phagocytosis of opsonized and nonopsonized particles and microbicidal activity of alveolar macrophages decreased significantly. The changes, though, were nearly twice as great as in patients who smoked. Gene expression of all proinflammatory cytokines in alveolar immune cells except interleukin 6 increased 2- to 20-fold over time in both groups. The expression of interleukin 1beta, interferon gamma, and tumor necrosis factor alpha, however, increased only half as much in smokers as in nonsmokers.

Conclusion

Smoking was associated with macrophage aggregation but markedly reduced phagocytic and microbicidal activity-possibly because expression of proinflammatory cytokines was reduced in these patients. Our data thus suggest that smokers may have a limited ability to mount an effective pulmonary immune defense after anesthesia and surgery.
Sinus Nodal Function and Risk for Atrial Fibrillation after Coronary Artery Bypass Graft Surgery
Authors: Hogue Charles W. , Filos Kriton S. , Schuessler Richard B. , Sundt Thoralf M.
Published: August 2004

Background

Nonsurgical patients with sinus node dysfunction are at high risk for atrial tachyarrhythmias, but whether a similar relation exists for atrial fibrillation after coronary artery bypass graft surgery is not clear. The purpose of this study was to evaluate sinus nodal function before and after coronary artery bypass graft surgery and to evaluate its relation with the risk for postoperative atrial arrhythmias.

Methods

Sixty patients without complications having elective coronary artery bypass graft surgery underwent sinus nodal function testing by measurement of sinoatrial conduction time (SACT) and corrected sinus nodal recovery time (CSNRT). Patients were categorized based on whether postoperative atrial fibrillation developed.

Results

Twenty patients developed atrial fibrillation between postoperative days 1 through 3. For patients remaining in sinus rhythm (n = 40), sinoatrial conduction times were no different and corrected sinus nodal recovery times were shorter after surgery when compared with measurements obtained after anesthesia induction. Sinus node function test results before surgery were similar between the sinus rhythm and the atrial fibrillation groups. After surgery, patients who later developed atrial fibrillation had longer sinoatrial conduction times compared with the sinus rhythm group (P = 0.006), but corrected sinus nodal recover time was not different between these groups. A sinoatrial conduction time > 96 ms measured at this time point was associated with a 7.3-fold increased risk of postoperative atrial fibrillation (sensitivity, 62%; specificity, 81%; positive and negative predictive values, 56% and 85%, respectively; area under the receiver operator characteristic curve, 0.72).

Conclusions

These data show that sinus nodal function is not adversely affected by uncomplicated coronary artery bypass surgery. Patients who later developed atrial fibrillation, however, had prolonged sinoatrial conduction immediately after surgery compared with patients remaining in sinus rhythm. These results suggest that injury to atrial conduction tissue at the time of surgery predisposes to postoperative atrial fibrillation and that assessment of sinoatrial conduction times could provide a means of identifying patients at high risk for postoperative atrial fibrillation.
Acoustic Reflectometry Profiles of Endotracheal and Esophageal Intubation
Authors: Raphael David T.
Published: August 2004

Background

Acoustic reflectometry can be used to create a "one-dimensional image" of a cavity, such as the airway and lung, with the image displayed as an area-length curve. This pilot study was undertaken to determine whether acoustic reflectometry could be used to distinguish between an endotracheal and an esophageal intubation.

Methods

Ten adult patients underwent general endotracheal anesthesia and neuromuscular blockade. The reflectometer wavetube was attached to an endotracheal tube, and a reflectometric profile was obtained of the endotracheal tube and the airway and lung cavity. After confirmation of tracheal intubation, a second endotracheal tube was placed in the esophagus. After four breaths were administered, a reflectometric profile of the endotracheal tube-esophagus cavity was obtained.

Results

The acoustic reflectometric profiles for tracheal and esophageal intubation profiles were distinctive and characteristic. For an endotracheal tube-airway cavity, the profile shows a constant cross-sectional area throughout the length of the endotracheal tube, followed by a rapid rise in the area past the carina. For an esophageal intubation, the profile shows constant cross-sectional area throughout the length of the endotracheal tube, followed by a sudden decrease in the cross-sectional area to zero.

Conclusions

In this pilot study, acoustic reflectometry within seconds, and without resort to capnography, was able to generate characteristic and distinctive area-length profiles for both endotracheal and esophageal intubation. Acoustic reflectometry may have a role in the emergency imaging of the airway, and in the immediate detection of esophageal intubations, particularly in cases of cardiopulmonary arrest in which the usual techniques for confirmation of breathing tube placement fail.
Changes in the Auditory Evoked Potentials and the Bispectral Index following Propofol or Propofol and Alfentanil
Authors: Iselin-Chaves Irene A. , El Moalem Habib E. , Gan Tong Joo , Ginsberg Brian , Glass Peter S. A.
Published: August 2004

Background

Midlatency auditory evoked potentials (MLAEP) show graded changes with increasing doses of hypnotics but little change with opioids. The effect of their combination on the MLAEP was evaluated. Also, the bispectral index (BIS) was compared with the ability of MLAEP to correlate with sedation and predict loss of consciousness.

Methods

Twenty healthy volunteers were randomly assigned to receive stepped increases in propofol concentration (10 subjects) or propofol plus alfentanil 100 ng/ml (10 subjects). At baseline and at each targeted effect site concentration the mean MLAEP, BIS, measures of sedation, and drug concentration were obtained. The relation among MLAEP, BIS, and sedation score was determined. The prediction probability (Pk) was calculated and compared for BIS and MLAEP.

Results

The BIS and MLAEP patterns showed significant changes (Pa and Nb decreased in amplitude and increased in latency) with increasing level of sedation (P < 0.0001). The BIS correlated better with sedation scores (0.884) than did the MLAEP (P < 0.05). Pa and Nb latencies showed the best correlation with sedation levels (0.685 and 0.658, respectively). The addition of alfentanil did not affect the relation between MLAEP and loss of consciousness (P > 0.15). The BIS (Pk = 0.952) was a better predictor of loss of consciousness than were Pa and Nb amplitude (P < 0.05) but were comparable to Pa and Nb latency (Pk = 0.869 and 0. 873, respectively).

Conclusion

MLAEP changes, like the BIS, correlate well with increasing sedation produced by propofol, and these changes in the MLAEP are independent of the presence of an opioid. Among all the MLAEP parameters, Pa and Nb latencies are the best predictors of increasing sedation and loss of consciousness.
Extent of Hyperbaric Spinal Anesthesia Influences the Duration of Spinal Block
Authors: Infante Nicoline E. Kooger , Van Gessel Elizabeth , Forster Alain , Gamulin Zdravko
Published: August 2004

Background

The influence of spread of spinal anesthesia on the duration of spinal blockade has been suggested but never investigated specifically. Because elimination of local anesthetic from subarachnoid space is probably dependent of the surface available for its diffusion and vascular absorption, the current study was designed to evaluate the hypothesis that with a same dose of hyperbaric bupivacaine, a higher anesthetic level would result in a shorter duration of spinal blockade than a lower level.

Methods

Three milliliters (15 mg) of hyperbaric bupivacaine, 0.5%, was injected intrathecally in 40 patients classified as American Society of Anesthesiologists physical status I or H scheduled for lower limb surgery during spinal anesthesia. To obtain significantly different anesthetic levels, the patients were positioned randomly either horizontally or with the torso elevated 30. Regression of sensory level and motor blockade, the appearance of pain at the operative site, and hemodynamic changes were evaluated.

Results

The maximum cephalad spread of sensory blockade (expressed as the median with ranges in parentheses) was significantly higher in the horizontal group than in the group with 30-degree elevation of the torso, i.e., T3.5 (T1-T9) versus T10 (T6-L1), with respectively significantly faster regression times (mean ¿ SD) by two segments (216 ¿ 46 mm vs. 253 ¿ 64 mm) and to segment L4 (269 ¿ 53 mm i s. 337 ¿ 58 mm), as well as shorter time to complete motor blockade recovery (173 ¿ 34 mm i s. 233 ¿ 58 mm) and faster appearance of pain at the operative site (221 ¿ 68 mm vs. 271 ¿ 56 mm).

Conclusion

The results indicate that with the same dose of hyperbaric bupivacaine, the duration of spinal blockade is longer in patients with restricted spread.
Isoflurane Delays but Does Not Prevent Cerebral Infarction in Rats Subjected to Focal Ischemia
Authors: Kawaguchi Masahiko , Kimbro J. Reed , Drummond John C. , Cole Daniel J. , Kelly Paul J. , Patel Piyush M.
Published: August 2004

Background

Several investigations have shown that volatile anesthetics can reduce ischemic cerebral injury. In these studies, however, neurologic injury was evaluated only after a short recovery period. Recent data suggest that injury caused by ischemia is a dynamic process characterized by continual neuronal loss for a prolonged period. Whether isoflurane-mediated neuroprotection is sustained after a longer recovery period is not known. The current study was conducted to compare the effect of isoflurane on brain injury after short (2-day) and long (14-day) recovery periods in rats subjected to focal ischemia.

Methods

Fasted Wistar-Kyoto rats were anesthetized with isoflurane and randomly allocated to an awake (n = 36) or an isoflurane (n = 34) group. Animals in both groups were subjected to focal ischemia by filament occlusion of the middle cerebral artery. Pericranial temperature was servocontrolled at 37 degrees C throughout the experiment. In the awake group, isoflurane was discontinued and the animals were allowed to awaken. In the isoflurane group, isoflurane anesthesia was maintained at 1.5 times the minimum alveolar concentration. After 70 min of focal ischemia, the filament was removed. Animals were killed 2 days (awake, n = 18; isoflurane, n = 17) and 14 days (awake, n = 18; isoflurane, n = 17) after ischemia. The volumes of cerebral infarction and selective neuronal necrosis in the animals were determined by image analysis of hematoxylin and eosin-stained coronal brain sections.

Results

Cortical and subcortical volumes of infarction were significantly less in the isoflurane 2-day group (26 +/- 23 mm3 and 17 +/- 6 mm3, respectively) than in the awake 2-day group (58 +/- 35 mm3, P < 0. 01; and 28 +/- 12 mm3, P < 0.01, respectively). By contrast, cortical and subcortical volumes of infarction in the awake (41 +/- 31 mm3 and 28 +/- 16 mm3, respectively) and isoflurane (41 +/- 35 mm3 and 19 +/- 8 mm3, respectively) 14-day groups were not different (cortex, P = 0.99; subcortex, P = 0.08). The volume of cortical tissue in which selective neuronal necrosis was observed, however, was significantly less in the isoflurane 14-day group (5 +/- 4 mm3) than in the awake 14-day group (17 +/- 9 mm3, P < 0.01). The total number of necrotic neurons in the region of selective neuronal necrosis was significantly smaller in the isoflurane 14-day group than in the awake 14-day group (P < 0.01).

Conclusion

Compared with the awake state, isoflurane reduced the extent of infarction assessed 2 days after focal ischemia in rats. At 14 days, however, only selective neuronal necrosis, but not infarction, was reduced by isoflurane. These results suggest that isoflurane delays but does not prevent cerebral infarction caused by focal ischemia. Isoflurane may attenuate the delayed development of selective neuronal necrosis in periinfarct areas in this animal model.
Anesthetics and Mild Hypothermia Similarly Prevent Hippocampal Neuron Death in an In Vitro Model of Cerebral Ischemia
Authors: Popovic Robert , Liniger Richard , Bickler Philip E.
Published: August 2004

Background

General anesthetics reduce neuron loss following focal cerebral ischemia in rodents. The relative efficacy of this action among different anesthetics clinically used for neuroprotection is uncertain. In addition, it remains unclear how anesthetics compare to neuroprotection afforded by mild hypothermia. This study was performed to evaluate the comparative effects of isoflurane, sodium pentothal, and mild hypothermia in a hippocampal slice model of cerebral ischemia and to determine if the mechanism of neuroprotection of isoflurane involves inhibition of glutamate excitotoxicity.

Methods

Survival and morphology of CA1, CA3, and dentate gyrus neurons in rat hippocampal slices were examined after 10 or 20 min of combined oxygen-glucose deprivation (in vitro ischemia) followed by a 5-h recovery period.

Results

10 or 20 min in vitro ischemia at 37 degrees C killed 35-40% of neurons in CA1 (P < 0.001), 6% in CA3 (not significant) and 18% in dentate (P < 0.05). Isoflurane (0.7 and 2.0%, approximately 0.45 and 1.5 minimum alveolar concentration), pentothal (50 microm, approximately 1 minimum alveolar concentration equivalent) and mild hypothermia (34 degrees C) all reduced CA1 cell loss and morphologic damage to similar degrees in 10- and 20-min periods of ischemia (P < 0.001). The noncompetitive N-methyl-D-aspartate antagonist MK-801 prevented cell damage, showing that N-methyl-D-aspartate receptor activation is an important mechanism of injury in this model. Glutamate (1 mm) produced cell loss similar to in vitro ischemia. Isoflurane (2%) prevented cell damage from glutamate exposure.

Conclusions

In hippocampal slices, neuron death from simulated ischemia was predominately due to activation of glutamate receptors. Isoflurane, sodium pentothal, an N-methyl-D-aspartate receptor antagonist, and mild hypothermia prevented cell death to similar degrees. For isoflurane, the mechanism appears to involve attenuation of glutamate excitotoxicity.
Spinal Tonicaine
Authors: Gerner Peter , Nakamura Tadashi , Quan Catherine F. , Anthony Douglas C. , Wang Ging Kuo
Published: August 2004

Background

Long-acting local anesthetics are beneficial for the management of postoperative pain and chronic pain. The authors recently reported that a single injection of N-beta-phenylethyl-lidocaine (tonicaine), a quaternary lidocaine derivative, effectively blocks rat sciatic nerve function four to nine times longer than lidocaine, with a predominance of sensory versusmotor blockade. The purposes of this study were to measure directly the potency of this charged drug by internal perfusion of cultured neuronal cells, and to evaluate the differential blockade of sensory versus motor function via spinal route in rats.

Methods

The tonic and additional use-dependent blockade of Na+ currents by internal tonicaine was assayed in cultured GH3 cells during whole cell voltage-clamp conditions. In addition, tonicaine was injected into the intrathecal space of rats at intervertebral space L4-L5, and the proprioceptive, motor, and sensory functions, and tissue integrity, subsequently were evaluated.

Results

Internal application of tonicaine in GH3 cells revealed that it was approximately 80 times more potent in blocking Na+ currents than was externally applied lidocaine. In vivotesting in a rat neuraxial anesthesia model showed that tonicaine at 0.5 mm produced blockade that lasted much longer than that produced by bupivacaine even at approximately a 55 times higher concentration (28.8 mm). Tonicaine spinal block also produced a longer duration of sensory than motor blockade (112.5 +/- 16.3 min vs. 45.8 +/- 7.1 min). Evidence of neurotoxicity was seen at a concentration of 1.0 mm.

Conclusion

In vitro testing shows that tonicaine displays a higher affinity for the local anesthetic binding site than does lidocaine; in vivotesting indicates that tonicaine elicits sensory blockade of a duration significantly longer than that elicited by bupivacaine. Tonicaine, however, has a narrow therapeutic index, with substantial neurotoxicity at 1 mm in rats, and may have limited clinical value.
FK506 (Tacrolimus) Increases Halothane-induced Ca2+Release from Skeletal Muscle Sarcoplasmic Reticulum
Authors: Chini Eduardo N. , Walker Henry
Published: August 2004

Background

FK506 binding protein is closely associated with the sarcoplasmic reticulum ryanodine receptor-channel and can modulate its function. The ryanodine receptor is stabilized by its association with FK506 binding protein. The immunosuppressant drugs FK506 (tacrolimus) and rapamycin can promote dissociation of FK506 binding protein from the ryanodine receptor 1 and by this mechanism increase sensitivity of ryanodine receptor 1 to agonists such as caffeine. Furthermore, it was shown recently that treatment of normal human skeletal muscle with FK506 and rapamycin increased halothane-induced contracture. The authors investigated the effect of the immunosuppressants FK506 and rapamycin on halothane-induced Ca2+ release in skeletal muscle sarcoplasmic reticulum vesicles.

Methods

Skeletal muscle terminal cisterns were isolated from New Zealand White rabbits. Ca2+ uptake and release was monitored in skeletal muscle sarcoplasmic reticulum vesicles using the fluo-3 fluorescent technique. Western Blot analysis of FK506 binding protein was performed using standard protocol.

Results

The authors observed that treatment of skeletal muscle sarcoplasmic reticulum vesicles with FK506 and rapamycin enhances halothane-induced Ca2+ release by about five times. Furthermore, the Ca2+ release induced by halothane in the presence of FK506 was inhibited by several antagonists of the ryanodine receptor, such as ruthenium red, spermine, and Mg2+.

Conclusion

Dissociation of FK506 binding protein from its binding site in skeletal muscle sarcoplasmic reticulum vesicles can modulate halothane-induced Ca2+ release through the ryanodine receptor. Data are discussed in relation to the role of the FK506 binding protein in modulating the effect of halothane on the ryanodine receptor and the development of malignant hyperthermia phenotype.
Rapid and Direct Modulation of GABAAReceptors by Halothane
Authors: Li Xiaoshen , Czajkowski Cynthia , Pearce Robert A.
Published: August 2004

Background

Hypotheses regarding the nature of channel modulation by volatile anesthetics have focused primarily on "membrane actions" of anesthetics and more recently on direct actions of volatile agents on receptor proteins themselves. With the recognition that many channels are subject to modulation by intracellular enzymes, such as protein kinases and phosphatases, and recent demonstrations that the activity of these modulators themselves may be altered by anesthetic agents, a third possibility has been suggested:-anesthetic actions on channels may be indirect, produced, for example, via direct effects on intracellular enzyme systems.

Methods

To determine the contribution of indirect versus direct modulation, the authors compared effects of the volatile anesthetic halothane on gamma-aminobutyric acid A receptors under two conditions: in the whole cell configuration with intact intracellular regulatory systems, and in the excised patch configuration, in which intracellular signaling systems have been disrupted. They also evaluated the effects of rapid application and withdrawal of anesthetic to determine the time course of onset and offset of the anesthetic actions on these channels.

Results

Characteristic changes in gamma-aminobutyric acid A receptor function occurred in excised patches as in whole cells, did not require alteration of receptor phosphorylation, and were rapid (onset and offset of anesthetic action occurred within milliseconds).

Conclusions

These results are not consistent with indirect modulation but rather indicate that volatile agents modulate gamma-aminobutyric acid A receptors by direct action on the channel complex or surrounding lipid membrane.
Intrathecal Dexmedetomidine Attenuates Hypercapnic but Not Hypoxic Cerebral Vasodilation in Anesthetized Rabbits
Authors: Takenaka Motoyasu , Iida Hiroki , Iida Mami , Dohi Shuji
Published: August 2004

Background

Systemic dexmedetomidine (DXM) attenuates the cerebral vasodilation induced by hypercapnia and decreases the cerebral blood flow response to hypoxia. We determined whether lumbar intrathecal DXM affected the cerebrovascular reactivity to hypercapnia and hypoxia.

Methods

Rabbits (n = 55) anesthetized with pentobarbital were prepared for measurement of pial vessel diameters using a closed cranial window preparation. The first study evaluated the response to hypercapnia after intrathecal administration of DXM (2 microg/kg; n = 7) or normal saline (n = 8). The second evaluated the response to hypercapnia after intrathecal DXM in the presence of yohimbine (20 microg/kg followed by DXM 2 microg/kg; n = 7). The third evaluated the response to mild or moderate hypoxia after intrathecal DXM (2 microg/kg; n = 7) or normal saline (n = 7). The hypercapnic responses were also examined in the presence of systemic DXM (2, 10 microg/kg; n = 6), topical DXM (10-8 m, 10-6 m; n = 6) and of intrathecal clonidine (2 microg/kg; n = 7).

Results

The pial arteriolar dilator response to hypercapnia was significantly attenuated after intrathecal administration of DXM. Pretreatment with yohimbine completely blocked the decreased reactivity to hypercapnia. Intrathecal clonidine, although less than DXM, also attenuate the hypercapnic response. Intrathecal DXM did not affect the vasodilation of pial arterioles induced by mild or moderate hypoxia. The systemic DXM 10 microg/kg and topical DXM 10-6 m, but not systemic 2 microg/kg and topical 10-8 m, attenuated hypercapnic vasodilation of pial arterioles.

Conclusions

The presence of alpha2-adrenoceptor agonist administered intrathecally into the lumbar spinal region attenuates hypercapnic but not hypoxic cerebral vasodilation, probably via a stimulation of central alpha2-adrenergic receptors of the central nervous system.
Opiate-induced Analgesia Is Increased and Prolonged in Mice Lacking P-glycoprotein
Authors: Thompson Susan J. , Koszdin Kari , Bernards Christopher M.
Published: August 2004

Background

P-glycoprotein is a transmembrane protein expressed by multiple mammalian cell types, including the endothelial cells that comprise the blood-brain-barrier. P-glycoprotein functions to actively pump a diverse array of xenobiotics out of the cells in which it is expressed. The purpose of this study was to determine if P-glycoprotein alters the analgesic efficacy of clinically useful opioids.

Methods

Using a standard hot-plate method, the magnitude and duration of analgesia from morphine, morphine-6-glucuronide, methadone, meperidine, and fentanyl were assessed in wild-type Friends virus B (FVB) mice and in FVB mice lacking P-glycoprotein [mdr1a/b(-/-)]. Analgesia was expressed as the percent maximal possible effect (%MPE) over time, and these data were used to calculate the area under the analgesia versus time curves (AUC) for all opioids studied. In addition, the effect of a P-glycoprotein inhibitor (cyclosporine, 100 mg/kg) on morphine analgesia in both wild-type and mdr knockout mice was also determined.

Results

Morphine induced greater analgesia in knockout mice compared with wild-type mice (AUC 6,450 %MPE min vs. 1,610 %MPE min at 3 mg/kg), and morphine brain concentrations were greater in knockout mice. Analgesia was also greater in knockout mice treated with methadone and fentanyl but not meperidine or morphine-6-glucuronide. Cyclosporine pretreatment markedly increased morphine analgesia in wild-type mice but had no effect in knockout mice.

Conclusions

These results suggest that P-glycoprotein acts to limit the entry of some opiates into the brain and that acute administration of P-glycoprotein inhibitors can increase the sensitivity to these opiates.
Isoflurane Preconditions Myocardium Against Infarction via Activation of Inhibitory Guanine Nucleotide Binding Proteins
Authors: Toller Wolfgang G. , Kersten Judy R. , Gross Eric R. , Pagel Paul S. , Warltier David C.
Published: August 2004

Background

Isoflurane-induced myocardial protection during ischemia is mediated by adenosine triphosphate-regulated potassium (KATP) channels; however, the intracellular signal transduction cascade responsible for this process has been incompletely evaluated. The authors tested the hypothesis that isoflurane reduces myocardial infarct size through a Gi protein-mediated process.

Methods

Forty-eight hours after pretreatment with vehicle (0.9% saline) or the Gi protein inhibitor pertussis toxin (10 microg/kg intravenously), barbiturate-anesthetized dogs (n = 43) were instrumented for measurement of aortic and left ventricular pressures and maximum rate of increase of left ventricular pressure. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3-h reperfusion. In four separate groups, vehicle- or pertussis toxin-pretreated dogs were studied with or without administration of 1 minimum alveolar concentration isoflurane. In two additional groups, dogs received the direct KATP channel agonist nicorandil (100 microg/kg bolus and 10 microg x kg-1 x min-1 intravenous infusion) in the presence or absence of pertussis toxin pretreatment. Myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively.

Results

Isoflurane significantly (P < 0.05) decreased infarct size to 7 +/- 2% of the area at risk compared with control experiments (26 +/- 2%). Pertussis toxin pretreatment alone had no effects on myocardial infarct size (31 +/- 4%) but blocked the beneficial effects of isoflurane (21 +/- 3%). Nicorandil decreased infarct size (11 +/- 2%), but, in contrast to isoflurane, this effect was independent of pertussis toxin pretreatment (11 +/- 1%).

Conclusion

Isoflurane reduces myocardial infarct size by a Gi protein-mediated mechanism in vivo.
Differential Neurotoxic Effects of Propofol on Dissociated Cortical Cells and Organotypic Hippocampal Cultures
Authors: Spahr-Schopfer Isabelle , Vutskits Lazlo , Toni Nicholas , Buchs Pierre-Alain , Parisi Lorena , Muller Dominique
Published: August 2004

Background

Propofol is a widely used anesthetic agent for adults and children. Although extensive clinical use has demonstrated its safety, neurologic dysfunctions have been described after the use of this agent. A recent study on a model of aggregating cell cultures reported that propofol might cause irreversible lesions of gamma-aminobutyric acid-mediated (GABAergic) neurons when administered at a critical phase of brain development. We investigated this issue by comparing the effects of long-term propofol treatment on two models of brain cultures: dissociated neonatal cortical cell cultures and organotypic slice cultures.

Methods

Survival of GABAergic neurons in dissociated cultures of newborn rat cortex (postnatal age, 1 day) treated for 3 days with different concentrations of propofol was assessed using histologic and cytochemical methods. For hippocampal organotypic slice cultures (postnatal age, 1 and 7 days), cell survival was assessed by measuring functional and morphologic parameters: extracellular and intracellular electrophysiology, propidium staining of dying cells, and light and electron microscopy.

Results

In dissociated neonatal cell cultures, propofol induced dose-dependent lesions of GABAergic neurons and of glial cells. In contrast, no evidence for neurotoxic effects of propofol were found after long-term treatment of organotypic slice cultures. Excitatory transmission was not affected by propofol, and inhibitory transmission was still functional. Histologic preparations showed no evidence for cell degeneration or death.

Conclusion

Although long-term applications of propofol to dissociated cortical cell cultures produced degeneration and death of GABAergic neurons and glial cells, no such lesions were found when using a model of postnatal organotypic slice cultures. This conclusion is based on both functional and morphologic tests.
The Action of Sevoflurane on Vascular Smooth Muscle of Isolated Mesenteric Resistance Arteries (Part 1)
Authors: Izumi Kaoru , Akata Takashi , Takahashi Shosuke
Published: August 2004

Background

The direct action of sevoflurane on systemic resistance arteries is not fully understood.

Methods

Isometric force was recorded in isolated rat small mesenteric arteries.

Results

Sevoflurane (2-5%) enhanced contractile response to norepinephrine only in the presence of endothelium, but inhibited it in its absence. Sevoflurane still enhanced the norepinephrine response after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of either endothelin-1 ET-1), angiotensin-II, or sevotonin receptors. Sevoflurane (3-5%) inhibited contractile response to potassium chloride only in the absence of endothelium but did not influence it in its presence. In the endothelium-intact strips, inhibition of the norepinephrine response, which was enhanced during application of sevoflurane, was observed after washout of sevoflurane and persisted for approximately 15 min. In the endothelium-denuded strips, the inhibition of norepinephrine response was similarly prolonged after washout of sevoflurane. However, no significant inhibitions of potassium chloride response were observed after washout of sevoflurane in both the endothelium-intact and the endothelium-denuded strips.

Conclusions

The action of sevoflurane on norepinephrine contractile response consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. In the presence of endothelium, the former predominates over the latter, enhancing the norepinephrine response. The endothelium-independent component persisted after washout of sevoflurane, leading to prolonged inhibition of the norepinephrine response. The mechanisms behind the sevoflurane-induced inhibition of norepinephrine response are at least in part different from those behind its inhibition of potassium chloride response. Nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, lipoxygenase products, endothelin-1, angiotensin-II, and serotonin are not involved in the vasoconstricting action. (Key words: Halogenated volatile anesthetics; sympathetic nervous system; systemic hypotension; vascular endothelium.)
Surgeon and Type of Anesthesia Predict Variability in Surgical Procedure Times
Authors: Strum David P. , Sampson Allan R. , May Jerrold H. , Vargas Luis G.
Published: August 2004

Background

Variability in surgical procedure times increases the cost of healthcare delivery by increasing both the underutilization and overutilization of expensive surgical resources. To reduce variability in surgical procedure times, we must identify and study its sources.

Methods

Our data set consisted of all surgeries performed over a 7-yr period at a large teaching hospital, resulting in 46,322 surgical cases. To study factors associated with variability in surgical procedure times, data mining techniques were used to segment and focus the data so that the analyses would be both technically and intellectually feasible. The data were subdivided into 40 representative segments of manageable size and variability based on headers adopted from the common procedural terminology classification. Each data segment was then analyzed using a main-effects linear model to identify and quantify specific sources of variability in surgical procedure times.

Results

The single most important source of variability in surgical procedure times was surgeon effect. Type of anesthesia, age, gender, and American Society of Anesthesiologists risk class were additional sources of variability. Intrinsic case-specific variability, unexplained by any of the preceding factors, was found to be highest for shorter surgeries relative to longer procedures. Variability in procedure times among surgeons was a multiplicative function (proportionate to time) of surgical time and total procedure time, such that as procedure times increased, variability in surgeons' surgical time increased proportionately.

Conclusions

Surgeon-specific variability should be considered when building scheduling heuristics for longer surgeries. Results concerning variability in surgical procedure times due to factors such as type of anesthesia, age, gender, and American Society of Anesthesiologists risk class may be extrapolated to scheduling in other institutions, although specifics on individual surgeons may not. This research identifies factors associated with variability in surgical procedure times, knowledge of which may ultimately be used to improve surgical scheduling and operating room utilization.
Validation of the Non-communicating Children's Pain Checklist–Postoperative Version
Authors: Breau Lynn M. , Finley G. Allen , McGrath Patrick J. , Camfield Carol S.
Published: August 2004

Background

This study evaluated the psychometric properties of the Non-communicating Children's Pain Checklist-Postoperative Version (NCCPC-PV) when used with children with severe intellectual disabilities.

Methods

The caregivers of 24 children with severe intellectual disabilities (aged 3-19 yr) took part. Each child was observed by one of their caregivers and one of the researchers for 10 min before and after surgery. They independently completed the NCCPC-PV and made a visual analog scale rating of the child's pain intensity for those times. A nurse also completed a visual analog scale for the same observations.

Results

The NCCPC-PV was internally reliable (Cronbach alpha = 0.91) and showed good interrater reliability. A repeated-measures analysis of variance indicated NCCPC-PV total and subscale scores were significantly higher after surgery and did not differ by observer. Postoperative NCCPC-PV scores correlated with visual analog scale ratings provided by caregivers and researchers, but not with those of nurses. A score of 11 on the NCCPC-PV, by caregivers, provided 0.88 sensitivity and 0.81 specificity for classifying children with moderate to severe pain.

Conclusions

The NCCPC-PV displayed good psychometric properties when used for the postoperative pain of children with severe intellectual disabilities and has the potential to be useful in a clinical setting. The results suggest familiarity with an individual child with intellectual disabilities is not necessary for pain assessment.
Chronobiology of Epidural Ropivacaine
Authors: Debon Richard , Chassard Dominique , Duflo Frédéric , Boselli Emmanuel , Bryssine Boris , Allaouchiche Bernard
Published: August 2004

Background

A temporal pattern of the kinetics of local anesthetics is demonstrated in dental and skin anesthesia, with an important variation in the duration of action related to the hour of administration. The aim of this study is to determine whether the hour of injection influences the duration of epidurally administered ropivacaine during labor.

Methods

One hundred ninety-four women in the first stage of labor were assigned to one of four groups throughout the day period: group 1 (night: from 1:01 to 7:00 am), group 2 (morning: from 7:01 am to 1:00 pm), group 3 (afternoon: from 1:01 to 7:00 pm), and group 4 (evening: from 7:01 pm to 1:00 am). Each patient received 14 ml ropivacaine, 0.17%, epidurally, and analgesia duration was measured.

Results

Pain assessed by a visual analog score was not differ-ent among groups before the first injection of local anesthetic. Analgesia duration was greater in the diurnal period (group 2: 110 +/- 25 min and group 3: 117 +/- 23 min) compared with the nocturnal period (group 1: 94 +/- 23 min and group 4: 91 +/- 23 min) (P < 0.01). The largest intraday variation of analgesia duration among groups reached 28%.

Conclusions

Epidural analgesia duration exhibits a temporal pattern with important differences among diurnal and nocturnal phases. The authors emphasize that the lack of consideration of the chronobiologic conditions in epidural analgesia studies may create significant statistical bias. Future studies dealing with epidural local anesthetics should consider the time of drug administration.
Cesarean Delivery
Authors: Sharma Shiv K. , Alexander James M. , Messick Gary , Bloom Steven L. , McIntire Donald D. , Wiley Jackie , Leveno Kenneth J.
Published: August 2004

Background

Controversy concerning increased cesarean births as a result of epidural analgesia for relief of labor pain has been attributed, in large part, to difficulties interpreting published studies because of design flaws. In this study, the authors compared epidural analgesia to intravenous meperidine analgesia using patient-controlled devices during labor to evaluate the effects of labor epidural analgesia, primarily on the rate of cesarean deliveries while minimizing limitations attributable to study design.

Methods

Four hundred fifty-nine nulliparous women in spontaneous labor at term were randomly assigned to receive either epidural analgesia or intravenous meperidine analgesia. Epidural analgesia was initiated with 0.25% bupivacaine and was maintained with 0.0625% bupivacaine and fentanyl 2 microg/ml at 6 ml/h with 5-ml bolus doses every 15 min as needed using a patient-controlled pump. Women in the intravenous analgesia group received 50 mg meperidine with 25 mg promethazine hydrochloride as an initial bolus, followed by 15 mg meperidine every 10 min as needed, using a patient-controlled pump. A written procedural manual that prescribed the intrapartum obstetric management was followed for each woman randomized in the study.

Results

A total of 226 women were randomized to receive epidural analgesia, and 233 women were randomized to receive intravenous meperidine analgesia. Protocol violations occurred in 8% (38 of 459) of women. There was no difference in the rate of cesarean deliveries between the two analgesia groups (epidural analgesia, 7% [16 of 226; 95% confidence interval, 4-11%] vs. intravenous meperidine analgesia, 9% [20 of 233; 95% confidence interval, 5-13%]; P = 0.61). Significantly more women randomized to epidural analgesia had forceps deliveries compared with those randomized to meperidine analgesia (12% [26 of 226] vs. 3% [7 of 233]; P < 0.001). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received intravenous meperidine analgesia.

Conclusions

Epidural analgesia compared with intravenous meperidine analgesia during labor does not increase cesarean deliveries in nulliparous women.
Inability to Consistently Elicit a Motor Response following Sensory Paresthesia during Interscalene Block Administration
Authors: Urmey William F. , Stanton Jennifer
Published: August 2004

Background

Two methods of nerve block based on eliciting neural feedback with the block needle currently exist. The paresthesia technique uses sensory feedback to ascertain that the needle tip is close to the nerve. By contrast, a peripheral nerve stimulator makes use of motor responses to electrical stimulation. The relation of motor responses to an electrical peripheral nerve stimulator and sensory nerve contact (paresthesia) had not been studied.

Methods

Thirty consecutive unpremedicated patients who presented for shoulder surgery with interscalene block anesthesia were prospectively studied. Interscalene block was performed by the single paresthesia method of Winnie, using an insulated or non-insulated needle connected to a peripheral nerve stimulator with the power off. At the precise point of paresthesia, the peripheral nerve stimulator was turned on, and the current was slowly increased to 1.0 mA with a pulse width of 0.2 ms. Presence and location of any motor responses were observed and recorded.

Results

All patients had easily elicited paresthesias. The site of first paresthesia was to the shoulder in 73% of patients. Only 30% of patients exhibited any motor response to electrical stimulation up to 1.0 mA. There was no relation between site of paresthesia and associated motor nerve response.

Conclusion

Elicitation of paresthesia does not translate to an ability to elicit a motor response to a peripheral nerve stimulator in the majority of patients.
The Influence of Remifentanil on the Dynamic Relationship between Sevoflurane and Surrogate Anesthetic Effect Measures Derived from the EEG
Authors: Olofsen Erik , Sleigh James W. , Dahan Albert
Published: August 2004

Background

The authors modeled the influence of remifentanil on the dynamics of sevoflurane using three parameters derived from the electroencephalogram: 95% spectral edge frequency (SEF), canonical univariate parameter (CUP), and Bispectral Index (BIS).

Methods

Thirty-six patients with American Society of Anesthesiologists physical status class I or II were recruited, of which 12 received a target remifentanil concentration of 0 ng/ml, eight 2 ng/ml, eight 4 ng/ml, and another eight 8 ng/ml. Next (before surgery), several step-wise changes in the end-tidal sevoflurane concentration (F(ET,sevo)) were performed. A data acquisition system simultaneously recorded F(ET,sevo), the raw electroencephalogram, BIS, and SEF. The authors used a combination of an effect compartment and an inhibitory sigmoid E(MAX) model to describe the relation between F(ET,sevo) and BIS, SEF, and CUP. Model parameters (t(1/2)k(e0), E(MAX), E(MIN), C(50), gamma, CUP weight factors) were estimated using the population data analysis program NONMEM. Significant remifentanil model parameter dependencies (P < 0.01) were determined.

Results

Determined from SEF, remifentanil had no effect on t(1/2)k(e0) (1.91 +/- 0.26 min [mean +/- standard error]) but caused an increase in C(50) (baseline = 1.48 +/- 0.12%; 80% increase at 8 ng/ml) and decrease in E(MIN) (baseline = 10.8 +/- 0.6 Hz; 80% reduction at 8 ng/ml). Determined from CUP, remifentanil caused a dose-dependent decrease in t(1/2)k(e0) (baseline = 4.31 +/- 1.00 min; 60% decrease at 8 ng/ml), with no effect on C(50) (baseline = 0.88 +/- 0.13%). Determined from BIS, remifentanil caused a dose-dependent decrease in t(1/2)k(e0) (baseline value = 3.11 +/- 0.32 min; 40% decrease at 8 ng/ml), without affecting C(50) (baseline = 1.12 +/- 0.05%). Median R(2) values of the pooled data set were 0.815 for SEF, 0.933 for CUP (P < 0.01 vs. SEF), and 0.952 for BIS (P < 0.01 vs. SEF and CUP). Addition of remifentanil increased the R(2) values for CUP only.

Conclusions

Remifentanil accelerates sevoflurane blood-brain equilibration without affecting its hypnotic potency as determined from BIS and CUP. In terms of R(2), the authors' pharmacodynamic model describes the anesthetic-BIS relation best.