bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Visual Analog Scale for Pain
Authors: Bodian Carol A. , Freedman Gordon , Hossain Sabera , Eisenkraft James B. , Beilin Yaakov 
Published: November 2003

Background
The visual analog scale is widely used in research studies, but its connection with clinical experience outside the research setting and the best way to administer the VAS forms are not well established. This study defines changes in dosing of intravenous patient-controlled analgesia as a clinically relevant outcome and compares it with VAS measures of postoperative pain.

Methods
Visual analog scale measurements were obtained from 150 patients on the morning after intraabdominal surgery. On the same afternoon, 50 of the patients provided a VAS score on the same form used in the morning, 50 on a new form, and 50 were not asked for a second VAS measurement.

Results
Visual analog scale values and changes in value were similar for patients who were given a new VAS form in the afternoon and those who used the form that showed the morning value. The proportions of patients requesting additional analgesia were 4, 43, and 80%, corresponding to afternoon VAS scores of 30 or less, 31-70, and greater than 70, respectively. Change from morning VAS score had no apparent influence on patient-controlled analgesic dosing for patients with afternoon values of 30 or less or greater than 70, but changes in VAS scores of at least 10 did discriminate among patients whose afternoon values were between 31 and 70.

Conclusions
When pain is an outcome measure in research studies, grouping final VAS scores into a small number of categories provides greater clinical relevance for comparisons than using the full spectrum of measured values or changes in value. Seeing an earlier VAS form has no apparent influence on later values.
Brain Expression of Inducible Cyclooxygenase 2 Messenger RNA in Rats Undergoing Cardiopulmonary Bypass
Authors: Hindman Bradley J. , Moore Steven A. , Cutkomp Johann , Smith Tom , Ross-Barta Susan E. , Dexter Franklin , Brian Johnny E. 
Published: November 2003

Background
We hypothesized that systemic proinflammatory cytokines or endotoxemia, or both, associated with cardiopulmonary bypass (CPB) would increase expression of inducible cyclooxygenase (COX-2) or inducible nitric oxide synthase (iNOS) messenger RNA (mRNA), or both, in brain.

Methods
Isoflurane-anesthetized Sprague-Dawley rats were randomly selected for CPB (n = 6) or sham surgery (n = 6). All animals underwent tracheotomy and controlled ventilation, arterial and venous pressure monitoring, insertion of a jugular venous outflow catheter, insertion of a subclavian arterial inflow catheter, systemic anticoagulation (500 U/kg heparin) and, except during CPB, servoregulation of pericranial temperature at 37.5 degrees C. Animals selected for CPB underwent 1 h of CPB at 165 ml x kg(-1) x min(-1) (31.8 +/- 0.2 degrees C), whereas animals having sham surgery underwent no intervention during this interval. Thereafter, all animals were given protamine and remained anesthetized for 4 more h. Brain and liver COX-2 and iNOS mRNA expression were determined by a ribonuclease protection assay with ribosomal L32 mRNA as a loading control. Arterial blood was analyzed for interleukin 1beta, interleukin 6, and endotoxin concentrations.

Results
Endotoxin concentrations did not increase above baseline values in either group. At 4 h after the CPB interval, interleukin 6 concentrations were significantly greater in CPB animals (101 +/- 45 pg/ml) versus sham animals (44 +/- 17 pg/ml) (P = 0.025). Brain COX-2 expression was significantly greater in CPB animals (0.36 +/- 0.11) versus shams (0.19 +/- 0.08) (P = 0.013). Brain COX-2 expression correlated with interleukin 6 concentration 4 h after CPB (r = 0.91; P = 5 x 10(-5)). In brain, iNOS mRNA was not detected in any animal. Cardiopulmonary bypass animals had only trace COX-2 and iNOS mRNA induction in liver.

Conclusions
Cardiopulmonary bypass was associated with increased systemic interleukin 6 concentrations and increased brain COX-2 expression.
Ketamine Blockade of Voltage-gated Sodium Channels
Authors: Wagner Larry E. , Gingrich Kevin J. , Kulli John C. , Yang Jay 
Published: November 2003

Background
The general anesthetic ketamine is known to be an N-methyl-D-aspartate receptor blocker. Although ketamine also blocks voltage-gated sodium channels in a local anesthetic-like fashion, little information exists on the molecular pharmacology of this interaction. We measured the effects of ketamine on sodium channels.

Methods
Wild-type and mutant (F1579A) recombinant rat skeletal muscle sodium channels were expressed in Xenopus oocytes. The F1579A amino acid substitution site is part of the intrapore local anesthetic receptor. The effect of ketamine was measured in oocytes expressing wild-type or mutant sodium channels using two-electrode voltage clamp.

Results
Ketamine blocked sodium channels in a local anesthetic-like fashion, exhibiting tonic blockade (concentration for half-maximal inhibition [IC50] = 0.8 mm), phasic blockade (IC50 = 2.3 mm), and leftward shift of the steady-state inactivation; the parameters of these actions were strongly modified by alteration of the intrapore local anesthetic binding site (IC50 = 2.1 mm and IC50 = 10.3 mm for tonic and phasic blockade, respectively). Compared with lidocaine, ketamine showed greater tonic inhibition but less phasic blockade.

Conclusions
Ketamine interacts with sodium channels in a local anesthetic-like fashion, including sharing a binding site with commonly used clinical local anesthetics.
Anesthetic Effects on Mitochondrial ATP-sensitive K Channel
Authors: Kohro Shinji , Hogan Quinn H. , Nakae Yuri , Yamakage Michiaki , Bosnjak Zeljko J. 
Published: November 2003

Background
Volatile anesthetics show an ischemic preconditioning-like cardioprotective effect, whereas intravenous anesthetics have cardioprotective effects for ischemic-reperfusion injury. Although recent evidence suggests that mitochondrial adenosine triphosphate-regulated potassium (mitoK(ATP)) channels are important in cardiac preconditioning, the effect of anesthetics on mitoK(ATP) is unexplored. Therefore, the authors tested the hypothesis that anesthetics act on the mitoK(ATP) channel and mitochondrial flavoprotein oxidation.

Methods
Myocardial cells were isolated from adult guinea pigs. Endogenous mitochondrial flavoprotein fluorescence, an indicator of mitochondrial flavoprotein oxidation, was monitored with fluorescence microscopy while myocytes were exposed individually for 15 min to isoflurane, sevoflurane, propofol, and pentobarbital. The authors further investigated the effect of 5-hydroxydeanoate, a specific mitoK(ATP) channel antagonist, on isoflurane- and sevoflurane-induced flavoprotein oxidation. Additionally, the effects of propofol and pentobarbital on isoflurane-induced flavoprotein oxidation were measured.

Results
Isoflurane and sevoflurane induced dose-dependent increases in flavoprotein oxidation (isoflurane: R2 = 0.71, n = 50; sevoflurane: R2 = 0.86, n = 20). The fluorescence increase produced by both isoflurane and sevoflurane was eliminated by 5-hydroxydeanoate. Although propofol and pentobarbital showed no significant effects on flavoprotein oxidation, they both dose-dependently inhibited isoflurane-induced flavoprotein oxidation.

Conclusions
Inhalational anesthetics induce flavoprotein oxidation through opening of the mitoK(ATP) channel. This may be an important mechanism contributing to anesthetic-induced preconditioning. Cardioprotective effects of intravenous anesthetics may not be dependent on flavoprotein oxidation, but the administration of propofol or pentobarbital may potentially inhibit the cardioprotective effect of inhalational anesthetics.
Inhalation Anesthetics Induce Apoptosis in Normal Peripheral Lymphocytes In Vitro
Authors: Matsuoka Hiroshi , Kurosawa Shin , Horinouchi Takashi , Kato Masato , Hashimoto Yasuhiko 
Published: November 2003

Background
The authors hypothesized that perioperative lymphocytopenia is partially caused by apoptosis of lymphocytes induced by inhalation anesthetics. Therefore, they evaluated whether sevoflurane and isoflurane induce apoptosis of normal peripheral lymphocytes.

Methods
Normal peripheral blood mononuclear cells were exposed to sevoflurane and isoflurane, and the percentages of apoptotic lymphocytes was measured by Annexin V-fluorescein isothiocyanate-7-amino actinomycin D flow cytometry after 24 h of exposure (0.5, 1.0, and 1.5 mm) and after 6, 12, and 24 h of exposure (1.5 mm). The percentages of lymphocytes with caspase 3-like activity were also measured after 24 h of exposure (1.5 mm).

Results
The percentages of apoptotic lymhocytes were increased in a dose-dependent manner (controls: 5.1 +/- 1.4%; sevoflurane: 7.3 +/- 1.3% [0.5 mm], 9.1 +/- 1.5% [1.0 mm], 12.6 +/- 2.1% [1.5 mm]; isoflurane: 7.5 +/- 1.6% [0.5 mm], 10.5 +/- 1.5% [1.0 mm], 16.3 +/- 2.7% [1.5 mm]) after 24 h of exposure and in a time-dependent manner (controls: 1.2 +/- 0.4% [6 h], 3.4 +/- 0.7% [12 h], 5.6 +/- 1.2% [24 h]; sevoflurane: 1.8 +/- 0.4% [6 h], 6.4 +/- 1.2% [12 h], 11.3 +/- 2.2% [24 h]; isoflurane: 2.6 +/- 0.5% [6 h], 8.8 +/- 1.5% [12 h],16.0 +/- 1.9% [24 h]) at the concentration of 1.5 mm. The percentages of lymphocytes with caspase 3-like activity were increased (controls: 10.0 +/- 1.1%; sevoflurane: 13.8 +/- 1.2%; isoflurane: 17.0 +/- 1.3%).

Conclusions
Both sevoflurane and isoflurane induced apoptosis in peripheral lymphocytes in dose-dependent and time-dependent manners in vitro.
Closed-loop Control of Anesthesia Using Bispectral Index
Authors: Absalom Anthony R. , Sutcliffe Nicholas , Kenny Gavin N. 
Published: November 2003

Background
The Bispectral Index (BIS) is an electroencephalogram-derived measure of anesthetic depth. A closed-loop anesthesia system was built using BIS as the control variable, a proportional-integral-differential control algorithm, and a propofol target-controlled infusion system as the control actuator. Closed-loop performance was assessed in 10 adult patients.

Methods
Ten adult patients scheduled to undergo elective hip or knee surgery were enrolled. An epidural cannula was inserted, and 0.5% bupivacaine was used to provide anesthesia to T8 before general anesthesia was induced using the propofol target-controlled infusion system under manual control. After the start of surgery, when anesthesia was clinically adequate, automatic control of anesthesia was commenced using the BIS as the control variable. Adequacy of anesthesia during closed-loop control was assessed clinically and by calculating the median performance error, the median absolute performance error, and the mean offset of the control variable.

Results
The median performance error and the median absolute performance error were 2.2 and 8.0%, respectively. Mean offset of the BIS from the set point was 0.9. Cardiovascular parameters were stable during closed-loop control. Operating conditions were adequate in all patients but one, who began moving after 45 min of stable anesthesia. No patients reported awareness or recall of intraoperative events. In three patients, there was oscillation of the measured BIS around the set point.

Conclusions
The system was able to provide clinically adequate anesthesia in 9 of 10 patients. Further studies are required to determine whether control performance can be improved by alterations to the gain factors or by using an effect site-targeted, target-controlled infusion propofol system.
Alveolar and Serum Procalcitonin
Authors: Duflo Frédéric , Debon Richard , Monneret Guillaume , Bienvenu Jacques , Chassard Dominique , Allaouchiche Bernard 
Published: November 2003

Background
The potential role of serum and alveolar procalcitonin as early markers of ventilator-associated pneumonia (VAP) and its prognostic value were investigated.

Methods
Ninety-six patients with a strong suspicion of VAP were prospectively enrolled. VAP diagnosis was based on a positive quantitative culture obtained via a mini-bronchoalveolar lavage of 103 colony-forming units/ml or more. Blood and alveolar samples were collected for procalcitonin measurement and analyzed for diagnostic and prognostic evaluation on days 0, 3, and 6. Sensitivity, specificity, positive likelihood ratio, and receiver-operating characteristic curves were analyzed to define ideal cutoff values and approach the decision analysis.

Results
Serum procalcitonin was significantly increased in the VAP group (n = 44) compared with the non-VAP group (n = 52): 11.5 ng/ml (95% confidence interval, 5.9-17.0) versus 1.5 ng/ml (1.1-1.9). A serum procalcitonin concentration greater than 3.9 ng/ml (best cutoff value) was considered positive for the VAP diagnosis (sensitivity, 41%; specificity, 100%). Serum procalcitonin was significantly increased in the non-survivors compared with the survivors for the VAP group: 16.5 ng/ml (95% confidence interval, 8.1-24.9) versus 2.9 ng/ml (1.2-4.7). The best cutoff value for serum procalcitonin of the nonsurvivors in the VAP group was 2.6 ng/ml (sensitivity, 74%; specificity, 75%; positive likelihood ratio, 2.96). Regarding VAP diagnosis and prognosis, no significant differences were found for alveolar procalcitonin in all groups.

Conclusions
Serum but not alveolar procalcitonin seems to be a helpful parameter in the early VAP diagnosis and an appropriate marker for predicting mortality.
Systemic Free Radical Activation Is a Major Event Involved In Myocardial Oxidative Stress Related to Cardiopulmonary Bypass
Authors: Clermont Gaëlle , Vergely Catherine , Jazayeri Saëd , Lahet Jean-Jacques , Goudeau Jean-Jacques , Lecour Sandrine , David Michel , Rochette Luc , Girard Claude 
Published: November 2003

Background
Cardiopulmonary bypass (CPB) can induce deleterious effects that could be triggered in part by radical oxygen species; however, their involvement in the course of surgery has been elusive. The aim of this study was to evaluate the time course and origin of radical oxygen species release, myocardial or not, in patients undergoing coronary artery surgery involving CPB.

Methods
Blood samples were taken from periphery and coronary sinus of patients during CPB, and oxidative stress was evaluated by direct and indirect approaches. Direct detection of alkyl and alkoxyl radicals was assessed by electron spin resonance spectroscopy associated with the spin-trapping technique using alpha-phenyl-N-tert-butylnitrone.

Results
The authors showed that the spin adduct concentration was not influenced by anesthesia and pre-CPB surgery. A rapid systemic increase of plasma spin adduct concentration occurred after starting CPB, and it stayed at a high concentration until the end of CPB. At the beginning of reperfusion period, radical oxygen species release was accelerated in the coronary sinus; however, it was not significant. A positive correlation was found between alpha-phenyl-N-tert-butylnitrone adduct concentrations and (1) the duration of CPB and (2) concentration of postoperative creatine phosphokinase of muscle band (CPK MB). Plasma vitamin E and C, ascorbyl radical, uric acid, thiol, plasma antioxidant status, and thiobarbituric acid reacting substances were also measured but did not give relevant indications, except for uric acid, which seemed to be consumed by the heart during reperfusion.

Conclusion
The results indicate that a systemic production of free radicals occurs during CPB that may overwhelm the production related to reperfusion of the ischemic heart. This systemic oxidative stress is likely to participate in secondary myocardial damage.
Effects of Parecoxib, a Parenteral COX-2-specific Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Propofol
Authors: Ibrahim Andra , Park Sang , Feldman Jennifer , Karim Aziz , Kharasch Evan D. 
Published: November 2003

Background
Parecoxib, a cyclooxygenase-2-specific inhibitor with intended perioperative analgesic and antiinflammatory use, is a parenterally administered inactive prodrug undergoing rapid hydrolysis in vivo to the active cyclooxygenase-2 inhibitor valdecoxib. Both parecoxib and valdecoxib inhibit human cytochrome P450 2C9 (CYP2C9) activity in vitro. Thus, a potential exists for in vivo interactions with other CYP2C9 substrates, including propofol. This investigation determined the influence of parecoxib on the pharmacokinetics and pharmacodynamics of bolus dose propofol in human volunteers.

Methods
This was a randomized, balanced crossover, placebo-controlled, double-blind, clinical investigation. Twelve healthy 21- to 37-yr-old subjects were studied after providing institutional review board-approved written informed consent. Each subject received a 2-mg/kg intravenous propofol bolus 1 h after placebo (control) or 40 mg intravenous parecoxib on two occasions. Venous concentrations of propofol, parecoxib, and parecoxib metabolites were determined by mass spectrometry. Pharmacokinetic parameters were determined by noncompartmental analysis. Pharmacodynamic measurements included clinical endpoints, cognitive function (memory, Digit-Symbol Substitution Tests), subjective self-assessment of recovery (Visual Analog Scale) performed at baseline, 15, 30, 60 min after propofol, and sedation depth measured by Bispectral Index.

Results
Propofol plasma concentrations were similar between placebo- and parecoxib-treated subjects. No significant differences were found in pharmacokinetic parameters (Cmax, clearance, elimination half-life, volume of distribution) or pharmacodynamic parameters (clinical endpoints [times to: loss of consciousness, apnea, return of response to voice], Bispectral Index scores, Digit-Symbol Substitution Test scores, memory, Visual Analog Scale scores, propofol EC(50)).

Conclusions
Single-bolus parecoxib, in doses to be used perioperatively, does not alter the disposition or the magnitude or time course of clinical effects of bolus propofol. Effects on a propofol infusion were not evaluated.
Effect of Ventilatory Settings on Accuracy of Cardiac Output Measurement Using Partial CO2Rebreathing
Authors: Tachibana Kazuya , Imanaka Hideaki , Miyano Hiroshi , Takeuchi Muneyuki , Kumon Keiji , Nishimura Masaji 
Published: November 2003

Background
Recently, a new device has been developed to measure cardiac output noninvasively using partial carbon dioxide (CO(2)) rebreathing. Because this technique uses CO(2) rebreathing, the authors suspected that ventilatory settings, such as tidal volume and ventilatory mode, would affect its accuracy: they conducted this study to investigate which parameters affect the accuracy of the measurement.

Methods
The authors enrolled 25 pharmacologically paralyzed adult post-cardiac surgery patients. They applied six ventilatory settings in random order: (1) volume-controlled ventilation with inspired tidal volume (V(T)) of 12 ml/kg; (2) volume-controlled ventilation with V(T) of 6 ml/kg; (3) pressure-controlled ventilation with V(T) of 12 ml/kg; (4) pressure-controlled ventilation with V(T) of 6 ml/kg; (5) inspired oxygen fraction of 1.0; and (6) high positive end-expiratory pressure. Then, they changed the maximum or minimum length of rebreathing loop with V(T) set at 12 ml/kg. After establishing steady-state conditions (15 min), they measured cardiac output using CO(2) rebreathing and thermodilution via a pulmonary artery catheter. Finally, they repeated the measurements during pressure support ventilation, when the patients had restored spontaneous breathing. The correlation between two methods was evaluated with linear regression and Bland-Altman analysis.

Results
When VT was set at 12 ml/kg, cardiac output with the CO(2) rebreathing technique correlated moderately with that measured by thermodilution (y = 1.02x, R = 0.63; bias, 0.28 l/min; limits of agreement, -1.78 to +2.34 l/min), regardless of ventilatory mode, oxygen concentration, or positive end-expiratory pressure. However, at a lower VT of 6 ml/kg, the CO(2) rebreathing technique underestimated cardiac out-put compared with thermodilution (y = 0.70x; R = 0.70; bias, -1.66 l/min; limits of agreement, -3.90 to +0.58 l/min). When the loop was fully retracted, the CO(2) rebreathing technique overestimated cardiac output.

Conclusions
Although cardiac output was underreported at small VT values, cardiac output measured by the CO(2) rebreathing technique correlates fairly with that measured by the thermodilution method.
Amitriptyline for Prolonged Cutaneous Analgesia in the Rat
Authors: Khan Mohammed A. , Gerner Peter , Kuo Wang Ging 
Published: November 2003

Background
Amitriptyline has been reported to be a more potent local anesthetic than bupivacaine. In keeping with the objective of identifying drugs for prolonged cutaneous analgesia, the authors compared the cutaneous analgesic effectiveness of amitriptyline and bupivacaine in rats.

Methods
Rats were subcutaneously injected on shaved dorsal skin. The skin wheal raised after injection of 0.6 ml of various concentrations of either amitriptyline or bupivacaine with and without epinephrine (1:200,000) was marked. Inhibition of the cutaneous trunci muscle reflex was evaluated quantitatively by the fraction of times a total of six pinpricks applied to the marked area failed to elicit a nocifensive motor response compared with control responses. No responses out of six pinpricks was defined as 100% maximum possible effect.

Results
Complete recovery from the cutaneous analgesia elicited by 0.05% and 0.5 amitriptyline versus 0.05 and 0.5% bupivacaine occurred in 9.9 +/- 0.2 and 19.3 +/- 0.4 h versus 2.2 +/- 0.1 and 16.1 +/- 0.2 h, respectively (mean +/- SE). Addition of epinephrine increased this duration to 14.1 +/- 0.1 and 21.4 +/- 0.2 h versus 3.2 +/- 0.1 and 17.0 +/- 0.3 h, respectively. Complete nociceptive blockade after coinjection of 0.25% amitriptyline, 0.25% bupivacaine, and epinephrine lasted 24 +/- 0.5 h, and complete recovery from this block took 33 +/- 0.5 h. Areas under the percent maximum possible effect versus time curve were 1,770 +/- 24 and 1,471 +/- 50% h for 0.5% amitriptyline and bupivacaine with epinephrine, respectively, whereas this value was 2,836 +/- 62% h for the coinjected 0.25% amitriptyline, 0.25% bupivacaine, and epinephrine admixture.

Conclusion
Amitriptyline is a longer-acting local anesthetic compared with bupivacaine for cutaneous infiltration. Its analgesic effectiveness is significantly enhanced by epinephrine. Coinjection of amitriptyline and bupivacaine with epinephrine enhances the analgesic duration of both drugs.