bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrasting Actions of Intrathecal U50, 488H, Morphine, or [D-Pen sup 2, D-Pen sup 5] Enkephalin or Intravenous U50, 488H on the Visceromotor Response to Colorectal Distension in the Rat
Authors: Harada Y. , Nishioka K. , Kitahata L. M. , Nakatani K. , Collins J. G.
Published: November 2003

Background

Visceral sensations are an important component of many clinical pain states. It is apparent that intrathecal pain relief may be more effective if appropriate combinations of drugs rather than a single agent can be used. The purpose of this study was to examine the relative contribution of opioid receptor subtypes to visceral antinociception using colorectal distension as a visceral pain model.

Methods

The minimum colorectal distending pressure necessary to evoke a visceromotor response (contraction of abdominal musculature) was determined before and after the administration of opioid agonists for the mu (morphine), delta ([D-Pen2, D-Pen5] enkephalin [DPDPE]), and kappa (U50,488H) opioid receptors. In addition to the three drugs administered intrathecally, U50, 488H was also administered intravenously.

Results

Morphine and DPDPE produced a reversible increase in threshold for activation of the visceromotor response (50% maximum possible effect [MPE] at intrathecal doses of 2.2 and 16.4 micrograms, respectively). The maximum intrathecal dose of U50,488H (100 micrograms) produced only a 20% MPE. Intravenous U50,488H produced a 50% MPE at a dose of 2.6 mg/kg.

Conclusions

The results suggest that spinal mu- and delta- but not kappa-opioid receptors have a significant role in the modulation of visceral nociception induced by colorectal distension. In addition, the results indicate that activation of nonspinal kappa receptors may mediate visceral antinociception.
Visceral Antinociceptive Effects of Spinal Clonidine Combined with Morphine, [D-Pen sup 2, D-Pen sup 5] Enkephalin, or U50,488H
Authors: Harada Y. , Nishioka K. , Kitahata L. M. , Kishikawa K. , Collins J. G.
Published: November 2003

Background

Visceral pain is an important component of many clinical pain states. The perispinal administration of drug combinations rather than a single agent may reduce side effects while maximizing analgesic effectiveness. The purpose of this study was to examine the nature of interactions between an alpha 2-adrenergic agonist (clonidine) and a mu-opioid agonist (morphine), a delta-opioid agonist ([D-Pen2, D-Pen5] enkephalin [DPDPE]), or a kappa-opioid agonist (U50,488H).

Methods

Colorectal distension was used to elicit a nociceptive visceromotor response (contraction of abdominal musculature) in rats. The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined.

Results

Clonidine produced dose-dependent reduction in threshold. U50,488H, at the doses tested, showed no synergistic interaction with clonidine.

Conclusions

Spinal combinations of alpha 2-adrenergic and mu- or delta- but not kappa-opioid agonists may be beneficial in the control of visceral pain.
Postoperative Pain Control with a New Transdermal Fentanyl Delivery System
Authors: Miguel Rafael , Kreitzer Joel M. , Reinhart Douglas , Sebel Peter S. , Bowie Julius , Freedman Gordon , Eisenkraft James B.
Published: November 2003

Background

A new transdermal delivery system for fentanyl is available in two strengths: 70-80 and 90-100 micrograms.kg-1.h-1 (40- and 60-cm2 patches, respectively). Their short onset and 24-h drug delivery make them attractive for postoperative pain control.

Methods

Both doses of the new transdermal fentanyl patches were evaluated for the relief of postoperative pain in 143 patients after gynecologic exploratory laparotomy. The study was conducted at four centers using a prospective, randomized, placebo-controlled, double-blind format. Patients were randomly assigned to one of three study groups: group 1 patients received two placebo patches: group 2 patients received a 40-cm2 fentanyl patch and a 60-cm2 placebo patch; and group 3 patients received a 60-cm2 fentanyl patch and a 40-cm2 placebo patch. Patient-controlled morphine use and pain, sedation, and comfort scores were assessed postoperatively every 4 h for 36 h after patch placement.

Results

Patients' assessment of their analgesia was significantly (P < or = 0.05) better in group 2 at 16 and 24 h and in group 3 at 8, 12, 16, 20, and 24 h postoperatively, compared with the patients in group 1. Patients in groups 2 and 3 required less supplemental morphine to maintain satisfactory analgesia than did the patients in group 1. Patients in groups 2 and 3 had greater incidences of pruritus, erythema, and respiratory depression than did those receiving placebo.

Conclusions

Concern exists regarding the side effects of this this new transdermal fentanyl patch. Therefore, this new patch will need further research before it can be recommended as an adjunct in controlling postoperative pain.
Influences of Subanesthetic Isoflurane on Ventilatory Control in Humans
Authors: van den Elsen Maarten , Dahan Albert , DeGoede Jacob , Berkenbosch Aad , van Kleef Jack
Published: November 2003

Background

The purpose of this study was to quantify in humans the effects of subanesthetic isoflurane on the ventilatory control system, in particular on the peripheral chemoreflex loop. Therefore we studied the dynamic ventilatory response to carbon dioxide, the effect of isoflurane wash-in upon sustained hypoxic steady-state ventilation, and the ventilatory response at the onset of 20 min of isocapnic hypoxia.

Methods

Study 1: Square-wave changes in end-tidal carbon dioxide tension (7.5-11.5 mmHg) were performed in eight healthy volunteers at 0 and 0.1 minimum alveolar concentration (MAC) isoflurane. Each hypercapnic response was separated into a fast, peripheral component and a slow, central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and off-set (apneic threshold). Study 2: The ventilatory changes due to the wash-in of 0.1 MAC isoflurane, 15 min after the induction of isocapnic hypoxia, were studied in 11 healthy volunteers. Study 3: The ventilatory responses to a step decrease in end-tidal oxygen (end-tidal oxygen tension from 110 to 44 mmHg within 3-4 breaths; duration of hypoxia 20 min) were assessed in eight healthy volunteers at 0, 0.1, and 0.2 MAC isoflurane.

Results

Values are reported as means +/- SF. Study 1: The peripheral carbon dioxide sensitivities averaged 0.50 +/- 0.08 (control) and 0.28 +/- 0.05 l.min-1.mmHg-1 (isoflurane; P < 0.01). The central carbon dioxide sensitivities (control 1.20 +/- 0.12 vs. isoflurane 1.04 +/- 0.11 l.min-1.mmHg-1) and off-sets (control 36.0 +/- 0.1 mmHg vs. isoflurane 34.5 +/- 0.2 mmHg) did not differ between treatments. Study 2: Within 30 s of exposure to 0.1 MAC isoflurane, ventilation decreased significantly, from 17.7 +/- 1.6 (hypoxia, awake) to 15.0 +/- 1.5 l.min-1 (hypoxia, isoflurane). Study 3: At the initiation of hypoxia ventilation increased by 7.7 +/- 1.4 (control), 4.1 +/- 0.8 (0.1 MAC; P < 0.05 vs. control), and 2.8 +/- 0.6 (0.2 MAC; P < 0.05 vs. control) l.min-1. The subsequent ventilatory decrease averaged 4.9 +/- 0.8 (control), 3.4 +/- 0.5 (0.1 MAC; difference not statistically significant), and 2.0 +/- 0.4 (0.2 MAC; P < 0.05 vs. control) l.min-1. There was a good correlation between the acute hypoxic response and the hypoxic ventilatory decrease (r = 0.9; P < 0.001).

Conclusions

The results of all three studies indicate a selective and profound effect of subanesthetic isoflurane on the peripheral chemoreflex loop at the site of the peripheral chemoreceptors. We relate the reduction of the ventilatory decrease of sustained hypoxia to the decrease of the initial ventilatory response to hypoxia.
Heat Balance and Distribution during the Core-Temperature Plateau in Anesthetized Humans
Authors: Kurz Andrea , Sessler Daniel I. , Christensen Richard , Dechert Martha
Published: November 2003

Background

Once triggered, intraoperative thermoregulatory vasoconstriction is remarkably effective in preventing further hypothermia. Protection results from both vasoconstriction-induced decrease in cutaneous heat loss and altered distribution of body heat. However, the independent contributions of each mechanism have not been quantified. Accordingly, we evaluated overall heat balance and distribution of heat within the body during the core-temperature plateau.

Methods

Nine minimally clothed male volunteers were anesthetized with propofol and isoflurane and maintained in an approximately 22 degrees C environment. They were monitored for approximately 2 h before vasoconstriction and for 3 h subsequently. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Arm and leg tissue heat contents were determined from 19 intramuscular temperatures, ten skin temperatures, and "deep" foot temperature. Heat constrained by vasoconstriction to the trunk and head was calculated by subtracting the expected change in that region (overall heat balance multiplied by the fractional weight of the trunk and head) from the actual change (change in distal esophageal temperature multiplied by the specific heat of human tissue and the weight of the trunk and head); the result represents the amount by which core heat exceeded that which would be expected based on overall heat balance, assuming that the change was evenly distributed throughout the body.

Results

Vasoconstriction and passive tissue cooling decreased heat loss but not to the level of heat production. Consequently, heat loss exceeded metabolic heat production throughout the study. Core temperature decreased approximately 1.3 C during the 2-h prevasoconstriction period; however, core temperature remained virtually constant during the subsequent 3 h. In the 3 h after vasoconstriction, arm and leg heat content decreased 57 +/- 9 kcal, and vasoconstriction constrained 22 +/- 8 kcal to the trunk and head.

Conclusions

These results confirm the efficacy of thermo-regulatory vasoconstriction in preventing additional core hypothermia. Decreased cutaneous heat loss and constraint of metabolic heat to the core thermal compartment contributed to the plateau.
Clinical Trial of a New Lightwand Device (Trachlight) to Intubate the Trachea
Authors: Hung Orlando R. , Pytka Saul , Morris Ian , Murphy Michael , Launcelott Gordon , Stevens Sarah , MacKay William , Stewart Ronald D.
Published: November 2003

Background

Transillumination of the soft tissue of the neck using a lighted stylet (lightwand) is an effective and safe intubating technique. A newly designed lightwand (Trachlight) incorporates modifications to improve the brightness of the light source as well as flexibility. The goal of this study was to determine the effectiveness and safety of this device in intubating the trachea of elective surgical patients.

Methods

Healthy surgical patients were studied. Patients with known or potential problems with intubation were excluded. During general anesthesia, the tracheas were intubated randomly using either the Trachlight or the laryngoscope. Failure to intubate was defined as lack of successful intubation after three attempts. The duration of each attempt was recorded as the time from insertion of the device into the oropharynx to the time of its removal. The total time to intubation (TTI), an overall measure of the ease of intubation, was defined as the sum of the durations of all (as many as three) intubation attempts. Complications, such as mucosal bleeding, lacerations, dental injury, and sore throat, were recorded.

Results

Nine hundred fifty patients (479 in the Trachlight group and 471 in the laryngoscope group) were studied. There was a 1% failure rate with the Trachlight, and 92% of intubations were successful on the first attempt, compared with a 3% failure rate and an 89% success rate on the first attempt with the laryngoscope (P not significant). All failures were followed by successful intubation using the alternate device. The TTI was significantly less with the Trachlight compared with the laryngoscope (15.7 +/- 10.8 vs. 19.6 +/- 23.7 s). For laryngoscopic intubation, the TTI was longer for patients with limited mandibular protrusion and mentohyoid distance, with a larger circumference of the neck, and with a high classification according to Mallampatti et al. However, there was no relation between the TTI and any of the airway parameters for Trachlight. There were significantly fewer traumatic events in the Trachlight group than in the laryngoscope group (10 vs. 37). More patients complained of sore throat in the laryngoscope group than in the Trachlight group (25.3% vs. 17.1%).

Conclusions

In contrast to laryngoscopy, the ease of intubation using the Trachlight does not appear to be influenced by anatomic variations of the upper airway. Intubation occasionally failed with the Trachlight but in all cases was resolved with direct laryngoscopy. The failures of direct laryngoscopy were resolved with Trachlight. Thus the combined technique was 100% successful in intubating the tracheas of all patients.
A System Model for Halothane Closed-Circuit Anesthesia
Authors: Vermeulen P. M. , Lerou J. G. C. , Dirksen R. , Booij L. H. D. J. , Borm G. F.
Published: November 2003

Background

Previously, the authors described a physiologic model for closed-circuit inhalational anesthesia. The basic version of this system model was clinically validated for isoflurane. An extended version adopted nonpulmonary elimination causing a constant fraction of anesthetic to be irreversibly lost. This version improved the accuracy of the model for enflurane. The model's performance for other inhalational anesthetics that are not biochemically inert, such as halothane, remained to be evaluated.

Methods

The current study quantified the predictive performance of four versions of the model by comparison of the predicted and measured alveolar halothane concentration-time profiles in 53 patients. Version A did not incorporate nonpulmonary elimination, whereas version D adopted a nonlinear hepatic nonpulmonary elimination following Michaelis-Menten kinetics. A and D used fixed partition coefficients. Their counterparts, A' and D', were formulated to examine the impact of age-adjusted partition coefficients on the accuracy of our model. Each concentration measured by mass spectrometry was compared to four predicted concentrations calculated by four computer simulations (one per version). For each patient, the authors calculated the root mean squared error (rmse; typical error size), bias (systematic component), and scatter of the prediction errors.

Results

Fifty-three patients were anesthetized with 330 ml of liquid halothane via 426 bolus injections during more than 61 h; 21,890 alveolar concentrations (average 0.6 vol%) were measured. Version D' showed the best overall performance with an rmse of 19.6 +/- 7.2%, a bias of 0.5 +/- 15.9%, and a scatter of 13.2 +/- 3.5% (mean +/- SD).

Conclusions

The model incorporating nonpulmonary elimination and age-adjusted partition coefficients (D') is sufficiently reliable and accurate to represent halothane closed-circuit anesthesia. This system model, with its various versions, is a valuable tool to predict the dynamics of isoflurane, enflurane, and halothane for clinical, educational, and research purposes.
Inhalation Anesthetics Inhibit the Release of Endothelium-derived Hyperpolarizing Factor in the Rabbit Carotid Artery
Authors: Lischke Volker , Busse Rudi , Hecker Markus
Published: November 2003

Background

Inhalation anesthetics may interfere with the synthesis or action of endothelium-derived vasoactive factors. We investigated the effects of desflurane, enflurane, halothane, isoflurane, and sevoflurane on the release of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) in the isolated endothelium-intact carotid artery of the rabbit.

Methods

Isolated segments of the carotid artery were suspended in Krebs-Henseleit solution (37 degrees C) and preconstricted with phenylephrine (1 microM). Relaxations caused by acetylcholine (ACh) (0.03-10 microM) or sodium nitroprusside (0.01-10 microM) were compared in the presence or absence of the nitric oxide synthase inhibitor NG-nitro-L-arginine (0.1 mM) in segments exposed to desflurane (8%), enflurane (2-4%), halothane (2-3.5%), isoflurane (2-4%), or sevoflurane (2%) as well as in NG-nitro-L- arginine-treated segments exposed to enflurane (2%) in combination with the KCa(+)-channel blocker tetrabutylammonium (0.3 mM) or the cytochrome P450 inhibitor clotrimazole (3 microM).

Results

Desflurane, enflurane, and sevoflurane selectively inhibited the ACh-induced release of EDHF. Halothane and isoflurane also weakly affected the nitric oxide-mediated relaxant response to ACh. The inhibitory effect of these two anesthetics on EDHF release was concentration-dependent. Relaxations induced by sodium nitroprusside were not inhibited by any of the anesthetics tested. Three structurally unrelated cytochrome P450 inhibitors clotrimazole (0.1 mM), metyrapone (1 mM), and SKF525a (proadifen, 0.1 mM) abolished the EDHF-mediated relaxation elicited by ACh. The pharmacologic profile of the inhibitory effect of enflurane on the release of EDHF closely resembled that of clotrimazole but not that of tetrabutylammonium. Moreover, all anesthetics inhibited the cytochrome P450-catalyzed O-dealkylation of 7-ethoxycoumarin by rabbit liver microsomes in a concentration-dependent manner.

Conclusions

Inhalation anesthetics significantly attenuate the EDHF-mediated relaxant response to ACh in the rabbit carotid artery. This effect appears to be attributable to inhibition of the cytochrome P450-dependent synthesis of EDHF by the endothelium.
Volatile Anesthetics Depress Calcium sup 2+ Transients and Glutamate Release in Isolated Cerebral Synaptosomes
Authors: Miao Ning , Frazer Martha J. , Lynch Carl III
Published: November 2003

Background

The current study was performed to determine whether volatile anesthetics may include as part of their action in the central nervous system the depression of presynaptic transmitter release by alteration in intrasynaptic [Ca2+] ([Ca2+]i).

Methods

Guinea pig cerebrocortical synaptosomes were studied at 37 degrees C suspended in control buffer solution containing 1.3 mM external [Ca2+] ([Ca2+]e). Spectrofluorometric assays were used to monitor [Ca2+]i with the Ca(2+)-sensitive fluorophore Fura-2 and to monitor glutamate release with an enzyme-coupled assay that produced the fluorescent product nicotinamide adenine dinucleotide phosphate. To activate the increase in [Ca2+]i and glutamate release, synaptosomes were depolarized by abruptly increasing external [K+] from 5 to 35 mM. Responses were determined in solutions equilibrated with approximately 1 or 2 minimum alveolar concentration (MAC) isoflurane, enflurane, or halothane and also in solutions with decreased [Ca2+]e (0.025, 0.05, 0.1, 0.2, 0.4, and 0.6 mM).

Results

Although they had no action on basal behavior, the anesthetics depressed the K(+)-depolarization-induced increase in both [Ca2+]i and glutamate release in a dose-dependent fashion. The [Ca2+]i transient was inhibited by 13-21% per MAC, and glutamate release was depressed 14-28% per MAC. The depression of both [Ca2+]i and glutamate release caused by 2.5% isoflurane, 3.4% enflurane, and 1.5% halothane could be reproduced by a reduction in [Ca2+]e to 0.2-0.4 mM.

Conclusions

In this setting, isoflurane, enflurane, and halothane decrease [Ca2+]i in a manner consistent with inhibition of Ca2+ entry, possibly by specific voltage-gated neuronal Ca2+ channels. This decrease in [Ca2+]i is sufficient to account for all or most of the associated decrease in glutamate release.
Preoperative Dipyridamole Thallium Imaging and Ambulatory Electrocardiographic Monitoring as a Predictor of Perioperative Cardiac Events and Long-term Outcome
Authors: Fleisher Lee A. , Rosenbaum Stanley H. , Nelson Ann H. , Jain Diwaker , Th Wackers Frans J. , Zaret Barry L.
Published: November 2003

Background

Dipyridamole thallium imaging (DTI) and ambulatory electrocardiography (AEGC) have been advocated as means to stratify risk before vascular surgery. The purpose of this study was to compare the predictive value of both tests in noncardiac surgery patients for perioperative cardiac morbidity and long-term mortality.
Pharmacokinetics of Computer-controlled Alfentanil Administration in Children Undergoing Cardiac Surgery
Authors: Fiset Pierre , Mathers Lawrence , Engstrom Ray , Fitzgerald David , Brand Stephen C. , Hsu Faye , Shafer Steven L.
Published: November 2003

Background

Cardiopulmonary bypass (CPB) induces changes in the pharmacokinetics of drugs. The purpose of this study was to model the pharmacokinetics of alfentanil in children undergoing cardiac surgery to provide accurate dosage titration intraoperatively as well as in the postoperative period.
Effect of Antiemetic Therapy on Recovery and Hospital Discharge Time
Authors: Davis Peter J. , McGowan Jr. Francis X. , Landsman Ira , Maloney Karen , Hoffmann Paul
Published: November 2003

Background

Postoperative nausea and vomiting continue to be a significant problem for pediatric ambulatory surgery patients. Although ondansetron has been demonstrated to be effective in the prophylactic treatment of postoperative nausea and vomiting (surrogate end point) no one has demonstrated a benefit of antiemetic therapy on patient recovery, postanesthesia care unit length of stay, and hospital length of stay (nonsurrogate end points). In a double-blind manner, the effects of ondansetron, droperidol, and placebo on the incidence of emesis, postanesthesia care unit stay, and hospital discharge time were evaluated in children undergoing dental surgery.
Measured Context-sensitive Half-times of Remifentanil and Alfentanil
Authors: Kapila Atul , Glass Peter S. A. , Jacobs James R. , Muir Keith T. , Hermann David J. , Shiraishi Masa , Howell Scott , Smith Richard L.
Published: November 2003

Background

The context-sensitive half-time, rather than the terminal elimination half-life, has been proposed as a more clinically relevant measure of decreasing drug concentration after a constant infusion of a given duration. The context-sensitive half-time is derived from computer modelling using known pharmacokinetic parameters. The modelled context-sensitive half-time for a 3-h infusion of alfentanil is 50–55 min and is 3 min for remifentanil. The terminal elimination half-life is 111 min for alfentanil and 12–30 min for remifentanil. It has not been tested whether the modelled context-sensitive half-time reflects the true time for a 50% decrease in drug concentration or drug effect.
Faster Recovery after Anesthesia in Infants after Intravenous Induction with Methohexital Instead of Thiopental
Authors: Beskow Annika , Werner Olof , Westrin Per
Published: November 2003

Background

To determine possible delays in recovery after intravenous anesthesia induction with thiopental, the drug was compared with methohexital in infants 1–12 months of age who were scheduled for hernia repair or circumcision.
Atracurium Versus Vecuronium in Asthmatic Patients
Authors: Caldwell James E. , Lau Marie , Fisher Dennis M.
Published: November 2003

Background

To determine which of atracurium or vecuronium is associated with fewer adverse cardiovascular and pulmonary events in high-risk patients, the authors administered these drugs to patients with known asthma.
Arteriovenous Differences in Plasma Concentrations of Catechols in Rats with Neuropathic Pain
Authors: Raja Srinivasa N. , Choi Yoon , Asano Yoshio , Holmes Courtney , Goldstein David S.
Published: November 2003

Background

Alterations in cutaneous temperature, sweating, and cutaneous blood flow in patients with pain states, such as reflex sympathetic dystrophy and causalgia, have been interpreted as evidence for exaggerated sympathetic outflow. It was determined whether pain behavior in a rat model of sympathetically maintained pain is associated with alterations in regional sympathoneural function.
Effects of Midazolam on Intracellular Calcium sup 2+ and Tension in Airway Smooth Muscles
Authors: Yoshimura Hayashi , Kai Tetsuya , Nishimura Junji , Kobayashi Sei , Takahashi Shosuke , Kanaide Hideo
Published: November 2003

Background

It has been demonstrated that a group of minor tranquilizers, benzodiazepines, are able to relax airway smooth muscles. To determine the underlying mechanisms of this phenomenon, the effects of midazolam on the intracellular Calcium2+ concentration ([Calcium2+]i) and tension in airway smooth muscles were investigated.
Intrathecal Amitriptyline
Authors: Eisenach James C. , Gebhart G. F.
Published: November 2003

Background

Systemically administered opioids induce analgesia in part by spinal noradrenergic, serotonergic, and cholinergic mechanisms. The current study tested whether antinociception from systemically administered opioids could therefore be enhanced by intrathecal injection of a monoamine reuptake inhibitor to potentiate the action of spinally released norepinephrine and serotonin (amitriptyline) and intrathecal injection of a cholinesterase inhibitor to potentiate the action of spinally released acetylcholine (neostigmine).
Intrathecal Amitriptyline Acts as an N-Methyl-D-Aspartate Receptor Antagonist in the Presence of Inflammatory Hyperalgesia in Rats
Authors: Eisenach James C. , Gebhart G. F.
Published: November 2003

Background

Amitriptyline and other tricyclic antidepressants exhibit high affinity binding to N-methyl-D-aspartate (NMDA) receptors in vitro and inhibit NMDA receptor activation-induced neuroplasticity in hippocampal slices. Because spinal NMDA receptor activation is believed to be central to generation and maintenance of hyperalgesic pain, the purpose of this study was to test whether intrathecal amitriptyline reduced inflammation-induced hyperalgesia in the rat.
One-day Hypothermic Preservation of Isolated Hearts with Halothane Improves Cardiac Function Better than Low Calcium
Authors: Stowe David F. , Habazettl Helmut , Graf Bernhard M. , Kampine John P. , Bosnjak Zeljko J.
Published: November 2003

Background

Halothane exerts a potent negative inotropic effect on the heart and mimics many of the cardiac effects of lowered extracellular CaCl2. Reduced slow inward Calcium2+ current and sarcoplasmic reticular effects on intracellular Calcium2+ are likely involved. The authors reported previously that halothane protects against hypoxic and ischemia reperfusion injury in isolated hearts. The aim of this isolated heart study was to compare protective effects of halothane and low CaCl sub 2 (0.5 mM) administered during 1 day of hypothermic perfusion on return of normothermic perfusion.
Epinephrine Is Metabolized by the Spinal Meninges of Monkeys and Pigs
Authors: Kern C. , Mautz D. S. , Bernards C. M.
Published: November 2003

Background

Epinephrine commonly is added to epidural opioids and local anesthetics, however, little is known about the fate of epidurally administered epinephrine. Studies have identified the epinephrine metabolizing enzyme, catechol-O-methyl transferase (COMT), in the cranial meninges of several species. The purpose of this study was to determine whether the spinal meninges also contain COMT and are capable of metabolizing epinephrine. If so, then the spinal meninges may have an important impact in limiting the bioavailability of epinephrine in both the spinal cord and epidural space.
Cardiovascular Stimulation Induced by Rapid Increases in Desflurane Concentration in Humans Results from Activation of Tracheopulmonary and Systemic Receptors
Authors: Weiskopf Richard B. , Eger II Edmond I. , Daniel Malcolm , Noorani Mariam
Published: November 2003

Background

It was hypothesized that stimulation of rapidly adapting airway receptors produces the transient (2–4 min) circulatory responses to rapid increases in desflurane concentrations greater than 6%. Accordingly, it was reasoned that increasing the concentration of desflurane in one lung, without altering the concentration of desflurane in systemic blood, should cause cardiovascular stimulation, whereas once the airway receptors had adapted to the stimulation, an initial increase in the systemic concentration of desflurane should have little effect.
Desflurane Slightly Increases the Sweating Threshold but Produces Marked, Nonlinear Decreases in the Vasoconstriction and Shivering Thresholds
Authors: Annadata Radhika , Sessler Daniel I. , Tayefeh Farzin , Kurz Andrea , Dechert Martha
Published: November 2003

Background

Shivering is rare during general anesthesia. This observation suggests that anesthetics profoundly impair shivering. However, the effects of surgical doses of volatile anesthetics on control of shivering have yet to be evaluated. Furthermore, the effects of desflurane on sweating and thermoregulatory vasoconstriction remain unknown. Accordingly, the authors determined the concentration-dependent effects of desflurane on sweating, vasoconstriction, and shivering.
Effect of Propofol on Spinal Dorsal Horn Neurons: Comparison with Lack of Ketamine Effects
Authors: Uchida Hiroshi , Kishikawa Kazuhiro , Collins J. G.
Published: November 2003

Background

Pentobarbital reduces low-threshold receptive field (RF) size and enhances responses of some spinal dorsal horn neurons to noxious stimulation in cats. To better understand the effects of general anesthetics on spinal sensory processing, this study was designed to determine if intravenous propofol and ketamine have similar effects.
Formal Instruction in Difficult Airway Management: A Survey of Anesthesiology Residency Programs
Authors: Koppel James N. , Reed Allan P.
Published: November 2003

Background

Up to 30% of all deaths attributable to anesthesia are related to difficulties with airway management. The purpose of this study was to determine whether anesthesiology residents are receiving specialized instruction in the various techniques and mechanical devices currently recommended for airway management in patients with anticipated or unanticipated difficult airways.
Differences in Respiratory Reflex Responses from the Larynx, Trachea, and Bronchi in Anesthetized Female Subjects
Authors: Nishino Takashi , Kochi Tetsuo , Ishii Masayuki
Published: November 2003

Background

Animal studies show that airway receptors responsible for eliciting respiratory protective reflexes are not uniformly distributed in the airways. Based on this information, it is possible that the protective reflex responses to airway irritation in humans may vary, depending on the site of stimulation. The purpose of this study is to examine whether the protective reflex responses evoked from the larynx are different from those evoked from the lower airways and to see how change in depth of anesthesia modifies the protective reflex responses evoked from individual sites.

Methods

The airway mucosa of the larynx, tracheal carina, and bronchi were stimulated by injection of distilled water (0.5 ml) at two different depths of sevoflurane anesthesia (1.2 and 1.8 MAC) in 11 female subjects breathing spontaneously through the laryngeal mask airway. The respiratory responses were monitored by measuring ventilatory flow and airway pressure.

Results

At 1.2 MAC of sevoflurane anesthesia, both laryngeal and tracheal stimulation caused protective responses, such as forceful expiratory efforts, apnea, and spasmodic panting, whereas bronchial stimulation caused little or no such responses. There was no significant difference in the incidence of different types of reflex responses between the larynx and the trachea. At 1.8 MAC of sevoflurane, the nature of the elicited responses was very similar to that observed at 1.2 MAC of sevoflurane, showing little dose-dependence of anesthetic effect.

Conclusions

The respiratory reflex responses evoked by injection of water vary, depending on the site of stimulation. The incidence of various reflex responses was not affected by the changing depth of anesthesia. The sensitivity to airway irritation seems to be greater at the larynx and trachea than at the more peripheral airways.
Propofol Fails to Attenuate the Cardiovascular Response to Rapid Increases in Desflurane Concentration
Authors: Daniel Malcolm , Eger Edmond I , Weiskopf Richard B. , Noorani Mariam
Published: November 2003

Background

A rapid increase in desflurane concentration to greater than 1 MAC transiently increases heart rate, arterial blood pressure, and circulating catecholamine concentration. Because propofol decreases sympathetic outflow, it was hypothesized that propofol would blunt these responses.

Methods

To test this hypothesis, five healthy male volunteers were studied three times. After induction of anesthesia with 2 mg.kg-1 propofol, anesthesia was maintained with 4% end-tidal desflurane in oxygen (0.55 MAC) via an endotracheal tube for 32 min. On separate occasions, in random order, either no propofol or 2 mg.kg-1 propofol was administered either 2 or 5 min before increasing end-tidal desflurane concentration from 4% to 8%.

Results

Without propofol pretreatment, the increase to 8% desflurane transiently increased heart rate (from 63 +/- 3 beats/min to 108 +/- 5 beats/min, mean +/- SEM; P < 0.01), mean arterial pressure (from 73 +/- 1 mmHg to 118 +/- 6 mmHg; P < 0.01), and epinephrine concentration (from 14 +/- 1 pg.ml-1 to 279 +/- 51 pg.ml-1; P < 0.05). There was no significant change in norepinephrine concentration (from 198 +/- 37 pg.ml-1 to 277 +/- 46 pg.ml-1). The peak plasma epinephrine concentration was attenuated by each propofol pretreatment (158 +/- 35 pg.ml-1, propofol given 2 min before, and 146 + 41 pg.ml-1, propofol given 5 min before; P < 0.05), but neither propofol pretreatment modified the cardiovascular or norepinephrine responses.

Conclusions

Although able to blunt the increase in epinephrine concentration, propofol 2 mg.kg-1 propofol does no attenuate the transient cardiovascular response to a rapid increase in desflurane concentration to greater than 1 MAC.
Pharmacokinetic Origin of Carbamazepine-induced Resistance to Vecuronium Neuromuscular Blockade in Anesthetized Patients
Authors: Alloul Karine , Whalley David G. , Shutway Fanny , Ebrahim Zeyd , Varin France
Published: November 2003

Background

Patients receiving chronic carbamazepine therapy have shortened recovery times from a neuromuscular block induced by vecuronium. The current study investigates the pharmacokinetic or pharmacodynamic mechanisms responsible for this observation.

Methods

Pharmacokinetics and pharmacodynamics of 0.1 mg/kg intravenous bolus vecuronium in ten epileptic patients receiving chronic carbamazepine therapy were compared to that of ten control subjects. All patients were scheduled for neurosurgery while anesthetized with isoflurane and sufentanil. Arterial blood samples were collected for 6 h. Plasma vecuronium concentrations were measured by high-performance liquid chromatography coupled to electrochemical detection. The adductor pollicis force of contraction was recorded after supramaximal ulnar nerve stimulation. Plasma vecuronium concentrations were fitted to a two-compartment pharmacokinetic model, and the effect compartment equilibration rate constant was derived with a nonparametric link model. The effect compartment concentrations were fitted to a sigmoid Emax model. Results were compared using Student's t-test for independent samples.

Results

In the carbamazepine group, the mean recovery times to T(1) 25% were shorter (28.1 +/- 3.4 vs. 47.3 +/- 5.1 min in control subjects; P=0.007), and the T(1) 25% to T(1) 75% recovery index was decreased (7.6 +/- 1.2 vs. 21.9 +/- 6.8 min in control subjects; P=0.025). No changes in onset times were observed. Clearance was 9.0 +/- 1.2 ml x kg-1 x min-1 versus 3.8 +/- 0.3 in the control group (P=0.003), whereas no changes in volumes of distribution at steady-state were observed. Therefore, the mean residence time was halved (17.8 +/- 2.5 vs. 31.9 +/- 2.5 min in control subjects; P=0.001). No differences in the effect compartment equilibration rate constant, vecuronium effect compartment concentration present at a 50% block (EC50), or slope of the sigmoid between the two groups were found.

Conclusions

The twofold increase in clearance provides evidence of a pharmacokinetic origin to the carbamazepine-vecuronium interaction; however, the possibility of a concurrent pharmacodynamic alteration cannot be assessed. Greater knowledge of protein drug binding needs to be acquired to give a meaningful interpretation to the similar EC50 values observed in the two groups.
Role of Magnesium Sulfate in Postoperative Analgesia
Authors: Tramer Martin R. , Schneider Jurg , Marti Rene-Andreas , Rifat Kaplan
Published: November 2003

Background

N-methyl-D-aspartate antagonists may play a role in the prevention of pain. An assessment was made of the effect of the physiologic N-methyl-D-aspartate antagonist magnesium on analgesic requirements, pain, comfort, and quality of sleep in the postoperative period.

Methods

In a randomized, double-blind study, 42 patients undergoing elective abdominal hysterectomy with general anesthesia received 20% magnesium sulfate or saline (control) 15 ml intravenously before start of surgery and 2.5 ml/h for the next 20 h. Postoperative morphine requirement was assessed for 48 h using patient-controlled analgesia. Maximum expiratory flow (peak flow), pain at rest and during peak flow, and discomfort were evaluated up to the 48th postoperative hour, and 1 week and 1 month after surgery. Insomnia was evaluated after the first and second postoperative nights.

Results

Compared to control subjects, magnesium-treated patients consumed less morphine during the first 48h (P<0.03), which was most pronounced during the first 6 h (P<0.004), and experienced less discomfort during the first and second postoperative days (P<0.05-0.005). The magnesium-treated group revealed no change in postoperative sleeping patterns when compared to preoperative patterns. Control patients showed an increase in insomnia during the first and second postoperative nights (P<0.002 and P<0.005, respectively) compared to preoperative values.

Conclusions

This is the first clinical study showing that the perioperative application of magnesium sulfate is associated with smaller analgesic requirement, less discomfort, and a better quality of sleep in the postoperative period but not with adverse effects. Magnesium could be of interest as an adjuvant to postoperative analgesia.
Plasma Inorganic Fluoride Concentrations after Sevoflurane Anesthesia in Children
Authors: Levine M. F. , Sarner J. , Lerman J. , Davis P. , Sikich N. , Maloney K. , Motoyama E. , Cook D. R.
Published: November 2003

Background

Sevoflurane is degraded in vivo in adults yielding plasma concentrations of inorganic fluoride [F-] that, in some patients, approach or exceed the 50- micron theoretical threshold for nephrotoxicity. To determine whether the plasma concentration of inorganic fluoride [F-] after 1-5 MAC x h sevoflurane approaches a similar concentration in children, the following study in 120 children scheduled for elective surgery was undertaken.

Methods

Children were randomly assigned to one of three treatment groups before induction of anesthesia: group 1 received sevoflurane in air/oxygen 30% (n = 40), group 2 received sevoflurane in 70% N2O/30% O2 (n = 40), and group 3 received halothane in 70% N2O/30% O2 (n = 40). Mapleson D or F circuits with fresh gas flows between 3 and 61/min were used Whole blood was collected at induction and termination of anesthesia and at 1, 4, 6, 12, and 18 or 24 h postoperatively for determination of the [F-]. Plasma urea and creatinine concentrations were determined at induction of anesthesia and 18 or 24 h postoperatively.

Results

The mean (+/- SD) duration of sevoflurane anesthesia, 2.7 +/- 1.6 MAC x h (range 1.1-8.9 MAC x h), was similar to that of halothane, 2.5 +/- 1.1 MAC x h. The peak [F-] after sevoflurane was recorded at 1 h after termination of the anesthetic in all but three children (whose peak values were recorded between 4 and 6 h postanesthesia). The mean peak [F-] after sevoflurane was 15.8 +/- 4.6 microns. The [F-] decreased to <6.2 microns b 24 h postanesthesia. Both the peak [F-] (r2 = 0.50) and the area under the plasma concentration of inorganic fluoride-time curve (r2 = 0.57) increased in parallel with the MAC x h of sevoflurane. The peak [F-] after halothane, 2.0 +/- 1.2 microns, was significantly less than that after sevoflurane (P<0.00012) and did not correlate with the duration of halothane anesthesia (MAC x h; r2 = 0.007). Plasma urea concentrations decreased 24 h after surgery compared with preoperative values for both anesthetics (P<0.01), whereas plasma creatinine concentrations did not change significantly with either anesthetic.

Conclusions

It was concluded that, during the 24 h after 2.7 +/- 1.6 MAC x h sevoflurane, the peak recorded [F-] is low (15.8 microns), F- is eliminated rapidly, and children are unlikely to be at risk of nephrotoxicity from high [F-].
Isoflurane and Sevoflurane Modulate Inactivation Kinetics of Calcium sup 2+ Currents in Single Bullfrog Atrial Myocytes
Authors: Hirota Koki , Fujimura Junko , Wakasugi Masahiro , Ito Yusuke
Published: November 2003

Background

To clarify the mechanism(s) of anesthetic depression of myocardial Ca2+ currents, the effects of isoflurane and sevoflurane on the inactivation kinetics of Ca2+ current in single bullfrog atrial myocytes were studied.

Methods

Freshly isolated bullfrog atrial myocytes were obtained with an enzymatic dispersion procedure. Ca2+ currents were recorded with a whole-cell voltage-clamp technique.

Results

Both isoflurane (1.25, 2.5, 5.0 vol%) and sevoflurane (2.5, 5.0 vol%) decreased the peak amplitude of Ca2+ current ICa with a minimal change in the time to peak and the reversal potential. The inactivation kinetics studies revealed that (1) isoflurane (2.5 vol%) and sevoflurane (5.0 vol%) markedly reduced the time constant of inactivation in ICa to 55% and 75% of control, respectively; (2) isoflurane (2.5 vol%) shifted the midpoint (V1/2) of steady-state inactivation curve of ICa toward negative by 2.3 mV; and (3) isoflurane (2.5 vol%) delayed the reactivation time constant of ICa to 119% of control. The further computer-simulation study demonstrated that the observed decrease of time constant by isoflurane (1.25, 2.5 vol%) and sevoflurane (2.5 vol%) can explain the reduction in amplitude of ICa.

Conclusions

The depression of ICa by lower concentration of isoflurane (1.25, 2.5 vol%) and sevoflurane (2.5 vol%) mainly is due to the decrease of time constant and, at higher concentration, isoflurane and sevoflurane may affect the other membrane components.
Prolonged d-Tubocurarine Infusion and/or Immobilization Cause Upregulation of Acetylcholine Receptors and Hyperkalemia to Succinylcholine in Rats
Authors: Yanez P. , Martyn J. A. J.
Published: November 2003

Background

Hyperkalemic cardiac arrest after the administration of succinylcholine (SCh) to critically ill intensive care patients has been attributed to changes in the acetylcholine receptors (AChRs) at the muscle membrane. The current study attempts to characterize the contributory roles of chronic administration of nondepolarizing muscle relaxants typified by d-tubocurarine (dTC) and/or of immobilization on AChR upregulation and the relationship of these AChR changes to SCh-induced hyperkalemia.

Methods

Rats received chronic subparalytic infusion of saline or dTC for 28 days via subcutaneous osmotic pumps inserted while they were under anesthesia. Approximately half of the saline- or dTC-treated rats underwent bilateral hind-limb immobilization with plaster casts for the same duration as the infusion. After 4 weeks, the osmotic pumps were removed, and 24-48 h later, the blood potassium concentrations were measured at baseline and at 1, 3, 5, 7, and 10 min after SCh (3 mg/kg). At the end of this period, the gastrocnemius muscle was excised for quantitation of AChR number using (125)I-alpha-bungarotoxin.

Results

At 28 days, the weight gain in mobile animals receiving saline or dTC infusion did not differ, nor did that in immobilized animals receiving saline or dTC infusion, confirming that infusion of dTC did not unduly affect the ability of the animals to feed. The maximal potassium change after SCh occurred at 5 min. Potassium responses to SCh changed (mean +/- SE): (1) from 3.9 +/- 0.04 to 4.5 +/- 0.1 mEq/1 in the mobile saline- treated control group, where the AChR concentration was 18.4 +/- 2 fmol/mg protein; (2) from 3.9 +/- 0.03 to 5.1 +/- 0.1 in the mobile dTC-infused group (AChRs = 48.6 +/- 7); (3) from 3.8 +/- 0.1 to 5.5 +/- 0.3 in the immobilized saline- treated group (AChRs = 107.4 +/- 14); and (4) from 3.8 +/- 0.1 to 6.3 +/- 0.2 in the immobilized-dTC-treated group (AChRs = 183.5 +/- 23). There was a significant positive correlation between maximal change in blood potassium concentration and the respective AChR concentration in the gastrocnemius of the same animal (r = 0.81, P<0.01).

Conclusions

Subtherapeutic (subparalytic) doses of chronic infusion of dTC (with no immobilization) or immobilization alone (with no dTC) independently increased number of AChRs. The infusion of dTC with immobilization caused the greatest upregulation of AChRs. The magnitude of the increase in blood potassium to SCh was directly dependent on AChR number. This study shows direct evidence and confirms previous speculation that AChR number plays an important role in the magnitude of the hyperkalemic response to SCh. Presuming this represents an appropriate model for patients who are immobilized and/or receiving nondepolarizing muscle relaxants for prolonged periods, exaggerated blood potassium responses to SCh are possible when either or both of these perturbations are present in patients.
Palmitoyl Carnitine Increases the Transmeningeal Flux of Hydrophilic but Not Hydrophobic Compounds In Vitro
Authors: Bernards Christopher M. , Kern Christian
Published: November 2003

Background

Increasing drug penetration through the spinal meninges should improve epidural analgesia/anesthesia by increasing the rate and extent to which epidurally administered drugs redistribute to the spinal cord. Palmitoyl carnitine has been shown to improve drug penetration through the intestinal mucosa. The purpose of this study was to determine whether palmitoyl carnitine improves drug penetration through the spinal meninges.

Methods

The transmeningeal flux of morphine, mannitol, bupivacaine, and sufentanil was determined through the spinal meninges of Macacca nemestrina monkeys before and after addition of palmitoyl carnitine. Flux was determined using a previously established in vitro diffusion cell method.

Results

Palmitoyl carnitine significantly increased the transmeningeal flux of mannitol, morphine, and bupivacaine by 942 +/- 102%, 401 +/- 43%, and 12 +/- 4%, respectively. However, palmitoyl carnitine had no significant effect on the transmeningeal flux of sufentanil. The penetration-enhancing effect of palmitoyl carnitine was shown to depend on the dose of palmitoyl carnitine added and on the octanol:buffer distribution coefficient of the study drugs but not on the concentration of the study drug.

Conclusions

The mechanism by which palmitoyl carnitine increases transmeningeal flux is unclear but may be a result of palmitoyl carnitine's ability to decrease packing order of lipid bilayers in the arachnoid mater cell membranes. Regardless of the mechanism, palmitoyl carnitine's ability to selectively increase the transmeningeal flux of hydrophilic compounds in vitro offers the possibility of improving the spinal bioavailability of this group of epidurally administered drugs in vivo.