bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isoflurane and Nociception
Authors: Kingery Wade S. , Agashe Geeta S. , Guo Tian Z. , Sawamura Shigehito , Frances Davies M. , David Clark J. , Kobilka Brian K. , Maze Mervyn 
Published: November 2003

Background
The authors recently established that the analgesic actions of the inhalation anesthetic nitrous oxide were mediated by noradrenergic bulbospinal neurons and spinal alpha2B adrenoceptors. They now determined whether noradrenergic brainstem nuclei and descending spinal pathways are responsible for the antinociceptive actions of the inhalation anesthetic isoflurane, and which alpha adrenoceptors mediate this effect.

Methods
After selective lesioning of noradrenergic nuclei by intracerebroventricular application of the mitochondrial toxin saporin coupled to the antibody directed against dopamine beta hydroxylase (DbetaH-saporin), the antinociceptive action of isoflurane was determined. Antagonists for the alpha1 and alpha2 adrenoceptors were injected at spinal and supraspinal sites in intact and spinally transected rats to identify the noradrenergic pathways mediating isoflurane antinociception. Null mice for each of the three alpha2-adrenoceptor subtypes (alpha2A, alpha2B, and alpha2C) and their wild-type cohorts were tested for their antinociceptive response to isoflurane.

Results
Both DbetaH-saporin treatment and chronic spinal transection enhanced the antinociceptive effects of isoflurane. The alpha1-adrenoceptor antagonist prazosin also enhanced isoflurane antinociception at a supraspinal site of action. The alpha2-adrenoceptor antagonist yohimbine inhibited isoflurane antinociception, and this effect was mediated by spinal alpha2 adrenoceptors. Null mice for the alpha2A-adrenoceptor subtype showed a reduced antinociceptive response to isoflurane.

Conclusions
The authors suggest that, at clinically effective concentrations, isoflurane can modulate nociception via three different mechanisms: (1) a pronociceptive effect requiring descending spinal pathways, brainstem noradrenergic nuclei, and supraspinal alpha1 adrenoceptors; (2) an antinociceptive effect requiring descending noradrenergic neurons and spinal alpha2A adrenoceptors; and (3) an antinociceptive effect mediated within the spinal cord for which no role for adrenergic mechanism has been found.
Efficient Trial Design for Eliciting a Pharmacokinetic– Pharmacodynamic Model–based Response Surface Describing the Interaction between Two Intravenous Anesthetic Drugs
Authors: Short Timothy G. , Ho Tam Yuk , Minto Charles F. , Schnider Thomas W. , Shafer Steven L. 
Published: November 2003

Background
The authors published a pharmacokinetic- pharmacodynamic model for two drugs based on response surface methodology. Because of the complexity of the model, they performed a simulation study to answer two questions about use of the model: (1) which study design would be most satisfactory; and (2) how many patients would need to be studied to adequately describe an entire response surface.

Methods
Data were simulated using realistic variability for two hypothetical intravenous anesthetic drugs that interact synergistically and that could be given by computer-controlled infusion. Three trial designs were simulated, one that made a series of parallel slices of the response surface, one that crisscrossed the response surface, and one that made a series of radial slices across the surface. Series of 5, 10, 20, and 40 "subjects" were simulated. A pooled data approach was used to assess the ability of the various trial designs and numbers of subjects to adequately identify the interaction response surface and estimate the original response surface.

Results
The crisscross design was shown to be the most robust in terms of its ability to both discriminate the correct order of the interaction term and to discriminate the original response surface using the least number of patients. Twenty subjects would be required to adequately define a surface using the crisscross study design, and 40 subjects would be required using the other trial designs.

Conclusions
The results showed that a number of trial designs would be viable, but a design that crossed the surface in a crisscross fashion would give the most robust result with the least patients.
Naloxone Improves Splanchnic Perfusion in Conscious Dogs through Effects on the Central Nervous System
Authors: Peter Weber Thomas , Meissner Andreas , Stypmann Jörg , Grosse Hartlage Maike , Van Aken Hugo , Rolf Norbert 
Published: November 2003

Background
In patients undergoing colonoscopy, naloxone has vasodilative properties. However, it remains unclear whether this effect is mediated by central or peripheral mechanisms. The aim of this study was to investigate whether these effects are mediated by an effect of naloxone on the central nervous system.

Methods
Twenty dogs were chronically instrumented for measurement of hemodynamic parameters. Splanchnic blood flow was determined using colored microspheres. Transthoracic echocardiographic examinations were performed to measure cardiac output. In each animal, two experiments were performed in a random order: experiment 1 was determination of splanchnic blood flow before and 5 min after intravenous administration of naloxone (63 microg/kg), and experiment 2 was determination of splanchnic blood flow before and 5 min after administration of naloxone methiodide (63 microg/kg), which does not cross the blood-brain barrier.

Results
Naloxone, but not naloxone methiodide, significantly increased blood flow to the stomach (from 0.41 +/- 0.022 to 0.9 +/- 0.016# ml x g (-1) x min(-1) with naloxone), jejunum (from 0.31 +/- 0.024 to 0.83 +/- 0.083# ml x g(-1) x min(-1) with naloxone), colon (from 0.41 +/- 0.057 to 0.68 +/- 0.008# ml x g(-1) x min(-1) with naloxone), spleen (from 1.45 +/- 0.21 to 2.13 +/- 0.25# ml x g(-1) x min(-1) with naloxone), pancreas (from 0.97 +/- 0.021 to 1.25 +/- 0.005# ml x g(-1) x min(-1) with naloxone), and kidneys (from 3.24 +/- 0.108 to 5.31 +/- 0.26# ml x g(-1) x min(-1) with naloxone), without altering cardiac output or arterial blood pressure in conscious dogs. There were no differences in the hemodynamics or cardiac output between the two experiments. Data are presented as mean +/- SD.

Conclusions
The increased splanchnic perfusion after naloxone is not caused by direct peripheral vascular effects or increased cardiac output. Indirect vasodilative effects on splanchnic vessels mediated by actions of naloxone on the central nervous system account for the increased gastrointestinal perfusion after naloxone in dogs.
Dextromethorphan and Memantine in Painful Diabetic Neuropathy and Postherpetic Neuralgia
Authors: Sang Christine N. , Booher Susan , Gilron Ian , Parada Suzan , Max Mitchell B. 
Published: November 2003

Background
There are few repeated dose-controlled trials of N-methyl-d-aspartate glutamate receptor antagonists in patients with neuropathic pain. The authors sought to evaluate two low-affinity N-methyl-d-aspartate antagonists using a novel two-stage design.

Methods
The authors studied patients with painful diabetic neuropathy (DN) and postherpetic neuralgia (PHN) in two crossover trials: (1) efficacy trial (dextromethorphan vs. memantine vs. active placebo [lorazepam]) and (2) dose-response trial of the preferred active drug in responders from the first study (0% vs. 25% vs. 50% vs. 100% of each patient's maximally tolerated dose). Pain intensity was measured on a 20-point scale.

Results
Nineteen of 23 DN patients and 17 of 21 PHN patients completed the efficacy trial. Median doses for DN and PHN were 400 and 400 mg/day dextromethorphan, 55 and 35 mg/day memantine, and 1.8 and 1.2 mg/day lorazepam. In the efficacy trial, among patients with DN, dextromethorphan reduced pain intensity by a mean of 33% from baseline, memantine reduced pain intensity by a mean of 17%, and lorazepam reduced pain intensity by a mean of 16%; the proportions of subjects achieving greater than moderate pain relief were 68% with dextromethorphan, 47% with memantine, and 37% with lorazepam. Mean reductions in pain intensity in patients with PHN were 6% with dextromethorphan, 2% with memantine, and 0% with lorazepam. No comparison with placebo reached statistical significance in the efficacy trial. In the 10 DN subjects who responded to dextromethorphan, there was a significant dose-response effect on pain intensity (P = 0.035), with the highest dose significantly better than that of lorazepam (P = 0.03).

Conclusions
Dextromethorphan is effective in a dose-related fashion in selected patients with DN. This was not true of PHN, suggesting a difference in pain mechanisms. Selective approaches to pain-relevant N-methyl-d-aspartate receptors are warranted.
Pharmacokinetics of Bupivacaine during Postoperative Epidural Infusion
Authors: Veering Bernadette Th. , Burm Anton G. L. , Feyen Hilde-Marieken , Olieman Wim , M. Souverijn John H. , van Kleef Jack W. 
Published: November 2003

Background
Changing plasma protein concentrations may affect the protein binding and pharmacokinetics of drugs in the postoperative period. This study examined the effect of postoperative increases (in response to surgery) in plasma alpha1-acid-glycoprotein (AAG) concentrations on the plasma concentrations of the enantiomers of bupivacaine during continuous epidural infusion of racemic bupivacaine for postoperative pain relief.

Methods
Six patients scheduled for total hip surgery with combined epidural and general anesthesia received a bolus dose of bupivacaine (65 mg) followed by constant-rate (8 ml/h) epidural infusion of 2.5 mg/ml bupivacaine for 48 h. Total and unbound plasma concentrations of the enantiomers of bupivacaine and plasma AAG concentrations during the 48-h epidural infusion were determined.

Results
Total plasma concentrations of the enantiomers of bupivacaine increased steadily during the infusion (P < 0.0001), whereas unbound concentrations did not change after 12 h (P > 0.1). Total plasma concentrations of S(-)-bupivacaine were higher than those of R(+)-bupivacaine (P < 0.02), whereas unbound concentrations of S(-)-bupivacaine were lower than those of R(+)-bupivacaine (P < 0.002). AAG concentrations initially decreased, but thereafter increased steadily (P < 0.0001). Consequently, free fractions of the enantiomers initially increased and then decreased with time (P = 0.0002). Free fractions of S(-)-bupivacaine were smaller than those of R(+)-bupivacaine (P = 0.0003).

Conclusions
The study confirmed that the pharmacokinetics of bupivacaine are enantioselective. During postoperative epidural infusion, changing plasma AAG concentrations affect the protein binding of both enantiomers of bupivacaine. Consequently, total plasma concentrations of the enantiomers increase with time, whereas unbound concentrations reach a plateau.
A Comparison of Intrathecal Fentanyl and Sufentanil for Labor Analgesia
Authors: Nelson Kenneth E. , Rauch Traci , Terebuh Victor , D'Angelo Robert 
Published: November 2003

Background
The use of intrathecal opioids for labor analgesia continues to gain popularity, but there are limited data to guide this use. Previously, the authors established the ED50 for 60 min of labor analgesia from intrathecal sufentanil using an up-down sequential allocation study design. The current study first establishes an ED50 for intrathecal fentanyl using this same study design to establish an intrathecal potency ratio for fentanyl and sufentanil and then uses this ratio to compare the efficacy, duration of analgesia, and side effects from comparable doses of intrathecal fentanyl and sufentanil.

Methods
Seventy-five healthy nulliparous women requesting labor analgesia were enrolled in this two-part study. In phase I, 20 women received varying doses of fentanyl to establish an ED50 for 60 min of labor analgesia. In phase II, 55 women were randomized to receive either 36 microg intrathecal fentanyl or 8 microg sufentanil (2 times the ED50s) via a combined spinal-epidural technique and by double-blinded design. Pain relief, side effects, block height, maternal hemodynamics, and fetal heart rate were assessed throughout the study. The duration of spinal analgesia was considered to be the time from injection of study drug to the time of the patient's first request for additional analgesia.

Results
The ED50 of intrathecal fentanyl for 60 min of labor analgesia was found to be 18.2 microg, and therefore, the potency ratio of intrathecal sufentanil to intrathecal fentanyl at the ED50 level is 4.4:1. The duration of spinal analgesia was significantly longer from 8 microg intrathecal sufentanil than from 36 microg intrathecal fentanyl (104 +/- 34 vs. 79 +/- 34 min, P = 0.009). Otherwise, patient demographics, maternal hemodynamics, duration of labor, mode of delivery, motor block, subjective leg weakness, pruritus, nausea, pinprick sensory levels, visual analog scale pain scores, fetal bradycardia, and Apgar scores were similar between groups.

Conclusion
The relative potency of intrathecal sufentanil to fentanyl for labor analgesia is 4.4:1. When using intrathecal opioids alone for early labor analgesia, 8 microg sufentanil produces labor analgesia lasting approximately 25 min longer than from 36 microg fentanyl, without a statistically significant increase in side effects. However, when making a choice between fentanyl and sufentanil, one must consider other important factors, such as the higher cost of sufentanil and the greater risk of dosing error due to the higher potency of sufentanil compared with fentanyl.
The Influence of Cuff Volume and Anatomic Location on Pharyngeal, Esophageal, and Tracheal Mucosal Pressures with the Esophageal Tracheal Combitube
Authors: Keller Christian , Brimacombe Joseph , Boehler Micheal , Loeckinger Alexander , Puehringer Friedrich 
Published: November 2003

Background
The authors determined the influence of cuff volume and anatomic location on pharyngeal, esophageal, and tracheal mucosal pressures for the esophageal tracheal combitube.

Methods
Twenty fresh cadavers were studied. Microchip sensors were attached to the anterior, lateral, and posterior surfaces of the distal and proximal cuffs of the small adult esophageal tracheal combitube. Mucosal pressure for the proximal cuff in the pharynx was measured at 0- to 100-ml cuff volume in 10-ml increments, and for the distal cuff in the esophagus and trachea were measured at 0- to 20-ml cuff volume in 2-ml increments. The proximal cuff volume to form an oropharyngeal seal of 30 cm H2O was determined. In addition, mucosal pressures for the proximal cuff in the pharynx were measured in four awake volunteers with topical anesthesia.

Results
There was an increase in mucosal pressure in the trachea, esophagus, and pharynx at all cuff locations with increasing volume (all: P < 0.001). Pharyngeal mucosal pressures were highest posteriorly (50-ml cuff volume: 99 +/- 62 cm H2O; 100-ml cuff volume: 255 +/- 161 cm H2O). Esophageal mucosal pressures were highest posteriorly (10-ml cuff volume: 108 +/- 55 cm H2O; 20-ml cuff volume: 269 +/- 133 cm H2O). Tracheal mucosal pressures were highest anteriorly (10-ml cuff volume: 98 +/- 53 cm H2O; 20-ml cuff volume: 236 +/- 139 cm H2O). The proximal cuff volume to obtain an oropharyngeal seal of 30 cm H2O was 47 +/- 12 ml. Pharyngeal mucosal pressures were similar for cadavers and awake volunteers.

Conclusion
We conclude that mucosal pressures for the esophageal tracheal combitube increase with cuff volume, are highest where the cuff is adjacent to rigid anatomic structures, and potentially exceed mucosal perfusion pressure even when cuff volumes are limited to achieving an oropharyngeal seal of 30 cm H2O.
Neutrophil Adhesion Molecule Expression and Serum Concentration of Soluble Adhesion Molecules during and after Pediatric Cardiovascular Surgery with or without Cardiopulmonary Bypass
Authors: Hambsch Jörg , Osmancik Pavel , Bocsi József , Schneider Peter , Tárnok Attila 
Published: November 2003

Background
Increased neutrophil activation by cardiopulmonary bypass (CPB) during cardiovascular surgery is thought to be responsible for postoperative complications. In children, the contribution of cardiovascular surgery alone to this response is not well-characterized.

Methods
Children undergoing surgery with CPB (CPB group, n = 35) and without CPB (control, n = 22) were studied (age, 3-17 yr). Blood was drawn 24 h preoperatively before medication, after anesthesia, after connection to CPB, at reperfusion, 4 h to 2 days after surgery, at discharge, and months after surgery. Neutrophil antigen expression and serum concentration of adhesion molecules, interleukin 8, and C5a (fragment of C5 complement) were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively.

Results
With and without CPB, anesthesia and surgery induced decreased LFA-1 (CD11a-CD18), Mac-1 (CD11b-CD18), CD45, and CD54 (intercellular adhesion molecule 1) surface expression and sICAM-1 serum concentrations (all P < 0.001). sL-selectin serum concentration decreased with CPB (P < 0.001) but was not significantly altered in the control. In contrast, CD62L expression increased during CPB (P < 0.001). The time course of all analyzed markers was not significantly different between CPB and control, with the exception of sL-selectin (P = 0.017). One-day preoperative baseline values were reached days to months after surgery. Interleukin 8 and C5a serum concentrations increased after surgery in both the CPB group and the control group.

Conclusions
Pediatric cardiovascular surgery leads to reduced adhesiveness and activity of circulating neutrophils. This reduction is more pronounced and sustained with CPB. These data may be useful in the assessment of novel therapeutic strategies.
Effects of Analgesics on Delayed Postherpetic Pain in Mice
Authors: Takasaki Ichiro , Sasaki Atsushi , Andoh Tsugunobu , Nojima Hiroshi , Shiraki Kimiyasu , Kuraishi Yasushi 
Published: November 2003

Background
Postherpetic neuralgia is pain that persists long after the disappearance of the cutaneous lesions of herpes zoster. However, the mechanisms of this delayed pain are unclear. Herpes simplex virus infection induces cutaneous lesions and pain-related responses in mice. The authors examined whether such responses would persist after the disappearance of the cutaneous lesions and whether some analgesics would be effective against them.

Methods
Female BALB/c mice were inoculated with herpes simplex virus type 1 on the unilateral hind paw. Pain-related responses of hind paw were determined using von Frey filaments. Beginning 5 days after inoculation, mice were given perorally the antiherpes agent acyclovir five times a day for 7 days. Effects of morphine (3-5 mg/kg subcutaneously), gabapentin (30-100 mg/kg perorally), mexiletine (10-30 mg/kg intraperitoneally), and diclofenac (30 mg/kg intraperitoneally) on pain-related responses were examined on days 25-35 after inoculation.

Results
Viral inoculation induced cutaneous lesions and pain-related responses beginning on day 5 after inoculation. Acyclovir treatment healed all skin lesions by day 15 after inoculation. Approximately half of the mice given acyclovir showed pain-related responses at least until day 40 after inoculation. Morphine, gabapentin, and mexiletine dose-dependently inhibited pain-related responses, but diclofenac had no effects.

Conclusions
The authors show a mouse model of delayed postherpetic pain. This may be useful for manifesting the mechanisms of postherpetic neuralgia and the factors contributing to the transition from acute herpetic pain to delayed postherpetic pain. This may also be useful for the development of new analgesics against postherpetic neuralgia.
What Sample Sizes are Required for Pooling Surgical Case Durations among Facilities to Decrease the Incidence of Procedures with Little Historical Data?
Authors: Dexter Franklin , Traub Rodney D. , Fleisher Lee A. , Rock Peter 
Published: November 2003

Background
Better predictions of each case's duration would reduce operating room labor costs and patient waiting times. A barrier to using historical case duration data to predict the duration of future cases is the absence for some cases of previous data for the same scheduled procedure from the same facility. The authors examined sample size requirements for pooling case duration data from several facilities to create a 90% chance of having case duration data for almost all procedures.

Methods
Four academic medical centers provided data, totaling 200,401 cases classified by the scheduled Current Procedural Terminology codes.

Results
The 12% of cases in which procedures occurred once or twice accounted for 79% of procedures or combinations of procedures. When a procedure was being performed for the first time at a facility, that same procedure had been performed previously at least once at one or more of the other three facilities only 13-25% of the time. More than 1 million cases would be needed to have a 90% chance of having at least 3 cases for each procedure observed in the original 200,401 cases. However, with N = 200,401 cases in our initial data set, we observed less than one third of the estimated total number of possible procedures.

Conclusions
The lack of historical case duration data for scheduled procedures is an important cause of inaccuracy in predicting case durations. However, millions of cases probably would be required to provide historical case duration data for almost all procedures.
Effect of Parecoxib, A Novel Intravenous Cyclooxygenase Type-2 Inhibitor, on the Postoperative Opioid Requirement and Quality of Pain Control
Authors: Tang Jun , Li Shitong , White Paul F. , Chen Xiaoguang , Wender Ronald H. , Quon Raymond , Sloninsky Alexander , Naruse Robert , Kariger Robert , Webb Tom , Norel Eve 
Published: November 2003

Background
The analgesic efficacy and side effect profile of intravenous parecoxib, a novel cyclooxygenase type-2 (COX-2) inhibitor, was assessed in a double-blinded, placebo-controlled study involving patients undergoing major gynecologic surgical procedures.

Methods
After Institutional Review Board approval, 60 consenting women, American Society of Anesthesiologists (ASA) physical status I-III, undergoing lower abdominal surgery with a standardized general anesthetic technique were randomly assigned to receive one of three study medications: group 1 (control) received normal saline; group 2 received intravenous parecoxib, 20 mg; and group 3 received intravenous parecoxib, 40 mg. The initial dose of study medication was administered when the patient first requested pain medication after surgery. All patients had access to patient-controlled analgesia (PCA) with intravenous morphine, 1 or 2 mg, with a 6-min lockout period. Subsequent doses of the same study medication were administered at 12-h and 24-h intervals after the initial dose. The postoperative opioid analgesic requirement (PCA morphine usage), pain scores, pain relief scores, side effects, and need for supplemental medications (e.g., antiemetics, antipruritics, laxatives) were recorded.

Results
Compared with saline, intravenous parecoxib, 20 mg and 40 mg every 12 h, significantly decreased the PCA morphine usage during the first 6 h postoperatively (group 1, 25 +/- 13 mg; group 2, 16 +/- 11 mg; group 3, 17 +/- 10 mg) and at 12 h (group 1, 34 +/- 18 mg; group 2, 24 +/- 14 mg; group 3, 23 +/- 13 mg) and 24 h (group 1, 51 +/- 27 mg; group 2, 34 +/- 20 mg; group 3, 33 +/- 21 mg) after surgery. However, there were no significant differences in the patients' global evaluation of the study medications at 12 h and 24 h between those who received intravenous parecoxib (20 or 40 mg) and saline. Moreover, the postoperative pain scores and side effect profiles were similar in the three treatment groups.

Conclusion
Intravenous parecoxib (20 or 40 mg) was effective in decreasing the PCA opioid requirement after lower abdominal surgical procedures. However, it failed to improve pain management or reduce opioid-related side effects in the early postoperative period.